Imidazopyrimidine derivatives and triazolopyrimidine derivatives

ABSTRACT

A compound of the formula (I) wherein R 1  is —X—R 4 , an optionally substituted heterocyclic residue, an optionally substituted carbocyclic residue or optionally substituted condensed ring moiety; X is CR 5 R 6 , O, S, SO, SO 2  or NR 7 ; Y is CH or N; R 2  is H, an optionally substituted C 1 -C 10  alkyl,etc.; R 3  is an optionally substituted aryl, or an optionally substituted heteroaryl, etc.; R 4  is an optionally substituted aryl, an optionally substituted heteroaryl, etc.; R 5 , R 6 , and R 7  can be identical or different and represent H, an optionally substituted C 1 -C 10  alkyl, etc. The compound has an excellent anti-allergic activity and the like.

TECHNICAL FIELD

[0001] The present invention relates to imidazopyrimidine derivativesand triazolopyrimidine derivatives, a process for the preparation of thederivatives and pharmaceutical preparations containing the derivatives.The imidazopyrimidine derivatives and triazolopyrimidine derivatives ofthe present invention inhibit Syk tyrosine kinase activity.

BACKGROUND ART

[0002] It is well known that the mast cells and basophils are theinitial players in the pathogenesis of allergic diseases, such asasthma, allergic rhinitis and atopic dermatitis.

[0003] The immediate type-I allergic reaction, such asbronchoconstriction in asthma, sneezing in allergic rhinitis and itchingin atopic dermatitis, are initiated by the interaction of antigens, suchas pollen or house dust, with their specific IgE captured on mast cellsand basophils. More specifically, high affinity IgE receptor (FceRI) onthe surface of mast cells and basophils traps IgE, which then recognizesantigen. Antigen-IgE interaction engages FceRI, resulting in elicitationof cellular response such as, histamine and PGD₂ release to cause theimmediate allergic reaction. Activated cells also produce leukotrienesand cytokines to cause the late inflammatory response, such as tissueeosinophilia.

[0004] Syk tyrosine kinase (Taniguchi, T. et. al., J. Biol. Chem. 266:15790-15796 (1991)) is one of tyrosine kinases involved in thesecellular responses. Costello, P. S. et. al. suggests that Syk tyrosinekinase is indispensable for the 3 cellular responses; degranulation,lipid mediator synthesis and cytokine production with the use of mastcells derived from syk knockout mice (Oncogene 13: 2595-2605 (1996)).Stenton, G. R. et. al. discloses that the Syk antisense oligo DNAinhalation suppress the parasite antigen-induced pulmonary inflammationin rats (J. Immunol., 164: 3790-3797 (2000)). Therefore, Syk tyrosinekinase inhibitors are expected to suppress both immediate allergicreaction and late inflammatory response.

[0005] Further, various genetic and pharmacological studies suggest Syktyrosine kinase plays important roles in other type of cells. Syk isreported to be essential for the FcγRs-mediated phagocytosis inmonocytes/macrophages (Matsuda, M. et. al., Mol. Biol. Cell 7: 1095-1106(1996)), pre BCR-mediated B cell maturation (Cornall, R. J. et. al.,Proc. Natl. Acad. Sci. USA 97: 1713-1718 (2000)), GM-CSF/IL-5-inducedeosinophil survival (Yousefi, S. et. al., J. Exp. Med., 183: 1407-1414(1996)), collagen-induced platelet activation (Poole, A. et. al., EMBOJ. 16: 2333-2341 (1997)), differentiation of fibroblast to adipocytes(Wang, H. and Malbon, C. C., J. Biol. Chem. 274: 32159-32166 (1999)) andβ-amyloid peptide-/prion peptide-induced neurotoxic product generationin microglia (Combs, C. K. et. al., J. Neurosci. 19: 928-939 (1999)).

[0006] Therefore, Syk tyrosine kinase inhibitors have possibilities toprevent antibody dependent cellular cytotoxicity (ADCC), antibodyrelated diseases, eosinophilic inflammation, platelet agglutination,obesity and Alzheimer/prion disease, respectively.

[0007] As an effective agent for a Syk inhibitor,pyrimidine-5-carboxyamide derivatives represented by general formula

[0008] wherein X^(d) represents O, S, NR^(1d), CO, NR^(1d)CO, CONR^(1d),C═N—OR^(1d) or a bond; Y^(d) represents lower alkylene optionallysubstituted by OR^(1d) or NHR^(1d) or a bond; Z^(d) represents O,NR^(2d) or attachment; A^(d) represents H, optionally substituted loweralkyl, lower alkyl optionally substituted by CO, optionally substitutedaryl, optionally substituted heteroaryl, optionally substitutedcycloalkyl or optionally substituted saturated heterocycle including N;B represents optionally substituted aryl or optionally substitutedheteroaryl; R^(1d) and R^(2d) represent H, lower alkyl, or —CO-loweralkyl, are disclosed in WO99/310773.

[0009] As an effective agent for a variety of diseases, variousimidazopyrimidine derivatives and triazolopyrimidine derivatives havebeen studied. For example, Abignente Enrico et al., (Farmaco (1991),46(10), 1099-110) discloses the compound of the following formula:

[0010] (wherein R^(1p) represents CO₂H, CO₂Et, CONH₂, CH₂CO₂H; R^(2p)represents Me, OMe; and R^(3p) represents OMe, Me, Cl) havinganti-inflammatory activity.

[0011] Danagulyan, G. G. et al., (Khim. Geterotsikl. Soedin. (1992),(2), 225-7) discloses the compounds of the following formula:

[0012] U.S. Pat. No. 4,639,445 discloses the compounds of the followingformula

[0013] wherein R^(e) is OH and n is 1 or 2, useful as bronchodilators.

[0014] U.S. Pat. No. 4,591,588 discloses the compounds of the followingformula

[0015] wherein n is 1 or 2, which shows bronchodilator activity.

[0016] However, none of the reference relating to imidazopyrimidinederivatives and triazolopyrimidine derivatives has aromatic group at C-7position nor suggest Syk tyrosine kinase inhibitory activity.

SUMMARY OF THE INVENTION

[0017] As a result of extensive studies on chemical modification ofimidazopyrimidine derivatives and triazolopyrimidine derivatives, thepresent inventors have found that the compounds of novel chemicalstructure related to the present invention have unexpectedly excellentSyk inhibitory activity. The present invention has been accomplishedbased on these findings.

[0018] This invention is to provide a novel compound shown by thefollowing general formula (I) and the salts thereof:

[0019] wherein R¹ represents —OR¹¹, —SR¹¹, —SOR¹¹, —SO₂R¹¹, —NHR¹¹,—NR¹²R¹³ or —CR¹⁴R¹⁵R¹¹,

[0020] R¹¹ represents H, phenyl carbonyl, thienyl optionally substitutedby COOR¹¹¹(R¹¹¹ is H or C₁-C₆ alkyl), pyrimidyl, C₂-C₆ alkenyl,imidazolyl optionally substituted by C₁-C₆ alkyl, triazolyl optionallysubstituted by C₁-C₆ alkyl, tetrazolyl optionally substituted by C₁-C₆alkyl, thiadiazolyl optionally substituted by C₁-C₆ alkyl, pyrrolidinyloptionally substituted by C₁-C₆ alkyl, cyclohexenyl, C₁-C₁₀ straight- orbranched-alkyl optionally substituted by R¹¹², R¹¹³ and/or R¹¹⁴, C₃-C₁₀cycloalkyl optionally substituted by R¹¹², R¹¹³ and/or R¹¹⁴, phenyloptionally substituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷, pyridyl optionallysubstituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷, or 9-10-membered unsaturatedcondensed ring which optionally contains up to 3 hetero atoms selectedfrom the group consisting of N, O and S and optionally substitued byR¹¹⁸,

[0021] R¹¹² represents halogen, amino, —COOR^(112a) (R^(112a) representsH or C₁-C₆ alkyl) —CO—NH—CH₃, —CO—NH—(CH₂)_(p)CN (wherein p representsinteger of 0-6), —NH—COOR^(112a), pyrazinyl, tetrazolyl,dihydrothiophenyl, morpholino, piperidino, di(C₁-C₆ alkyl)amino,indolyl, pyridinyl, thiophenyl, or phenyl optionally substituted by oneto three substituents selected from the group consisting of halogen,C₁-C₆ alkyl, hydroxy, C₁-C₆ alkoxy, and trihalogen substituted C₁-C₆alkyl,

[0022] R¹¹³ represents halogen, hydroxy, or C₁-C₆ alkoxy-carbonyl,

[0023] R¹¹⁴ represents halogen,

[0024] R¹¹⁵ represents H, halogen, amino, hydroxy, nitro, cyano, C₁-C₆alkoxy, carboxy, C₁-C₆ alkoxy carbonyl, C₁-C₆ alkyl carbonyl,morpholino-C₁-C₆ alkyl-oxy, caroboxy-C₁-C₆ alkyl-oxy, trihalogensubstituted methyl, trihalogen substituted methoxy, C₁-C₁₀ straight- orbranched-alkyl optionally substituted by R^(115a), C₃-C₁₀ cyclo-alkyloptionally substituted by R^(115a), tetrazolyl, amidino,—CON(R^(115b))R^(115c), —SO₂N(R^(115b))R^(115c), —N(R^(115b))R^(115c),—SO₂R^(115d), —SOR^(115d), —SR^(115d), or C₂-C₆ alkenyl optionallysubstituted by COOR^(115e),

[0025] R^(115a) represents one or two selected from the group consistingof carboxy, morpholino, morpholino-carbonyl, amino, hydroxy, cyano,C₁-C₆ alkoxy carbonyl, carbamoyl optionally substituted by cyano-C₁-C₆alkyl, methylamino-carbonyl, dimethylamino-carbonyl, —NH—SO₂—CH₃,tetrazolyl, dihydrooxazolyl optionally substituted by C₁-C₆ alkyl, and9-10 membered unsaturated condensed ring containing one N atomoptionally substituted by ═O,

[0026] R^(115b) represents H or C₁-C₆ alkyl,

[0027] R^(115c) represents H, amino, C₁-C₆ alkylamino, di(C₁-C₆alkyl)amino, amidino, morpholino-C₁-C₆ alkyl carbonyl, carboxy-C₁-C₆alkyl carbonyl, or straight- or branched C₁-C₆ alkyl optionallysubstituted by one or two selected from the group consisting of hydroxy,phenyl, morpholino, di(C₁-C₆ alkyl) amino, C₁-C₆ alkyl and hydroxyC_(l)-C₆ alkyl substituted amino, C₁-C₆ alkoxy-carbonyl, and carboxy,

[0028] or R^(115b) and R^(115c) together with the adjacent N form 5 or 6membered saturated hetero cyclic ring optionally having one N or O atomother than the adjacent N and optionally substituted by C₁-C₆ alkyl,

[0029] R^(115d) represents hydroxy, hydroxy C₁-C₆ alkyl, C₁-C₆ alkyl,hydroxy-carbonyl-C₁-C₆ alkyl, or C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl,

[0030] R^(115e) represents hydrogen or C₁-C₆ alkyl,

[0031] R¹¹⁶ represents H, C₁-C₆ alkoxy, C₁-C₆ alkyl, halogen, orcarbamoyl,

[0032] R¹¹⁷ represents H, halogen, or C₁-C₆ alkoxy,

[0033] R¹¹⁸ represents one to three substituents selected from the groupconsisting of C₁-C₆ alkyl, amino, C₁-C₆ alkoxy, —COOR^(118a) (H or C₁-C₆alkyl), and ═O,

[0034] R¹² represents C₁-C₆ alkyl, —(CH₂)_(n)—OH, —(CH₂)_(n)—CN (n=0, 1,2, 3, 4, 5, or 6), —CO—C₁-C₆ alkyl, or —C₂-C₆ alkenyl, R¹³ is identicalto R¹¹,

[0035] or R¹² and R¹³ together with the adjacent N atom form 4-6membered saturated heterocyclic ring which may or may not contain 1heteroatom other than the adjacent N atom selected from the groupconsisting of O, N, and S the 4-6 membered heterocyclic ring optionallyforms spiro with dioxacyclopentane, or is optionally fused with benzene,and/or is optionally substituted by one or two substituents selectedfrom the group consisting of C₁-C₆ alkyl carbonyl, C₁-C₆ alkyl, hydroxy,hydroxy C₁-C₆ alkyl, carboxyl, C₁-C₆ alkoxy carbonyl, carbamoyl, phenyl,halogen substituted phenyl, C₁-C₆ alkoxy substituted phenyl, C₁-C₆ alkylsubstituted phenyl, nitro phenyl, hydroxy phenyl, C₁-C6 alkyl carbonylphenyl, C₁-C₆ alkoxy carbonyl phenyl, pyridyl optionally substituted byCF₃, pyrimidyl, C₃₋₇ cycloalkyl, dioxolanyl, piperidino, halogensubstituted phenyl carbonyl, furyl carbonyl, cyano, dimethylamino,benzyl, oxo residue, piperonyl methyl, halogen substituted diphenylmethyl, and trifluorocarbonyl amino,

[0036] R¹⁴ and R¹⁵ are identical or different and represent H, C₁-C₁₀alkyl, hydroxy, hydroxy C₁-C₆ alkyl, cyano C₁-C₆ alkyl, C₃-C₁₀cycloalkyl, C₂-C₁₀ alkenyl, or C₁-C₆ alkyl carbonyl;

[0037] Y is CH or N;

[0038] R² is H, C₁-C₆ alkyl, carbamoyl, or —COOR²¹

[0039] wherein R²¹ is H or C₁-C₆ alkyl;

[0040] R³ is thienyl, pyridyl optionally substituted by halogen or C₁-C₆alkoxy, naphthyl optionally substituted by C₁-C₆ alkoxy, dioxane fusedphenyl, dioxacyclopentane fused phenyl, or phenyl optionally substitutedby one to three substituents selected from the group consisting ofhalogen, C₁-C₆ alkyl, nitro, amino, hydroxy, C₁-C₆ alkylthio, —OR³¹,OR³², —NR³³R³⁴, and —SO₂R³⁵,

[0041] wherein R³¹ and R³² are identical or different and representC₁-C₆ alkyl carbonyl, C₁-C₆ alkoxy carbonyl, C₂-C₆ alkenyl, di(C₁-C₆alkyl) amino carbonyl, C₁-C₆ alkyl amino carbonyl, —SO₂—R³¹¹, orstraight- or branched-C₁-C₆ alkyl optionally substituted by R³¹²,cyclo-C₃-C₇ alkyl optionally substituted by R³¹²,

[0042] R³¹¹ represents C₁-C₆ alkyl, amino, di(C₁-C₆ alkyl) amino C₁-C₆alkyl amino, C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl amino, or 5-6 memberedsaturated hetero cyclic ring containing up to 2 heteroatoms of N, S,and/or O and optionally substituted by C₁-C₆ alkyl or carboxy,

[0043] R³¹² represents C₁-C₆ alkoxy, halogen, phenyl optionallysubstituted by C₁-C₆ alkoxy, di(C₁-C₆ alkyl) amino, C₁-C₆ alkyl andhydroxy C₁-C₆ alkyl substituted amino, or 5-6 membered saturated heterocyclic ring containing up to 2 heteroatoms of N, S, and/or O andoptionally substituted by one or three substituents selected from thegroup consisting of C₁-C₆ alkyl, carbamoyl, and di(C₁-C₆ alkyl)amino,

[0044] R³³ represents H or C₁-C₆ alkyl,

[0045] R³⁴ represents carboxy C₁-C₆ alkyl carbonyl, C₁-C₆ alkylcarbonyl, or C₁-C₆ alkyl optionally substituted by R³⁴¹,

[0046] wherein R³⁴¹ represents dimethylamino, C₁-C₆ alkoxy, morpholino,phenyl, C₁-C₆ alkyl substituted piperazino, oxopyrrolidino, orimidazolyl,

[0047] or —N R³³R³⁴ forms 5-6-membered saturated hetero cyclic ringoptionally containing one more hetero atom selected from the groupconsisting of N, S, and O and optionally substituted by C₁-C₆ alkyl,

[0048] R³⁵ represents amino, di(C₁-C₆ alkyl)amino C₁-C₆, alkyl amino,piperazino optionally substituted by hydroxy C₁-C₆ alkyl or C₁-C₆ alkyl,C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl amino, morpholino, piperidinooptionally substituted by carboxy or C₁-C₆ alkyl, or hydroxy C₁-C₆ alkylamino,

[0049] or its tautomeric or stereoisomeric form, or its physiologicallyacceptable salt.

[0050] The compound of the present invention surprisingly show excellentSyk tyrosine kinase inhibitory activity. They are therefore suitableespecially as Syk tyrosine kinase inhibitors and in particular for theproduction of medicament or medical composition, which may be useful totreat Syk tyrosine kinase dependent diseases.

[0051] More specifically, since the compounds of the present inventioninhibit Syk tyrosine kinase activity, they are useful for treatment andprophylaxis of diseases involving Syk tyrosine kinase activity asfollows: those caused by allergic or inflammatory reaction which includeallergic diseases, such as asthma, allergic rhinitis, atopic dermatitis,food allergy, contact allergy, hives, conjunctivitis, and vernalcatarrh; autoimmune diseases, such as chronic arthrorheumatism, systemiclupus erythematosus, and psoriasis; diabrotic diseases includingdiabrotic colitis; fibrous diseases; tumor and the like.

[0052] The compounds of the present invention are also useful fortreatment and prophylaxis of diseases: those caused by immune reactionincluding rejections or graft versus host disease upon organtransplantation; those caused by antibody-dependent cellularcytotoxicity, such as autoimmune hemolytic anemia, myasthenia gravis;thrombus caused by platelet agglutination; obesity; and Alzheimerdisease, since all of the diseases described also relate to Syk tyrosinekinase activity.

[0053] Preferred compounds of formula (I) are those wherein:

[0054] R¹ is —OR¹¹, —SR¹¹, —NHR¹¹, or —NR¹²R¹³,

[0055] R¹¹ represents H, phenyl carbonyl, thienyl optionally substitutedby COOR¹¹¹ (R¹¹¹ is H or C₁-C₆ alkyl), pyrimidyl, C₂-C₆ alkenyl,imidazolyl optionally substituted by C₁-C₆ alkyl, triazolyl optionallysubstituted by C₁-C₆ alkyl, tetrazolyl optionally substituted by C₁-C₆alkyl, thiadiazolyl optionally substituted by C₁-C₆ alkyl, pyrrolidinyloptionally substituted by C₁-C₆ alkyl, cyclohexenyl, C₁-C₁₀ straight- orbranched-alkyl optionally substituted by R¹¹², R¹¹³ and/or R¹¹⁴, C₃-C₁₀cyclo-alkyl optionally substituted by R¹¹², R¹¹³ and/or R¹¹⁴, phenyloptionally substituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷, pyridyl optionallysubstituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷,or 9-10-membered unsaturatedcondensed ring which optionally contains up to 3 hetero atoms selectedfrom the group consisting of N and S and optionally substitued by R¹¹⁸,

[0056] R¹¹² represents halogen, amino, —COOR^(112a) (R^(112a) representsH or C₁-C₆ alkyl) —CO—NH—CH₃, —CO—NH—(CH₂)_(p)CN, —NH—COOR^(112a),pyrazinyl, tetrazolyl, dihydrothiophenyl, morpholino, piperidino,di(C₁-C₆ alkyl)amino, indolyl, pyridinyl, thiophenyl, or phenyloptionally substituted by one substituent selected from the groupconsisiting of halogen, hydroxy, C₁-C₆ alkoxy, and trihalogensubstituted methyl,

[0057] R¹¹³ represents halogen, hydroxy, or C₁-C₆ alkoxy-carbonyl,

[0058] R¹¹⁴ represents halogen,

[0059] R¹¹⁵ represents H, halogen, amino, hydroxy, nitro, cyano,carboxy, C₁-C₆ alkoxycarbonyl, C₁-C₆alkoxy, C₁-C₆ alkyl carbonyl,morpholino-C₁-C₆ alkyl-oxy, carboxy-C₁-C₆ alkyl-oxy, trihalogensubstituted methyl, trihalogen substituted methoxy, C_(l)-C₁₀ straight-or branched-alkyl optionally substituted by R^(115a), C₃-C₁₀ cyclo-alkyloptionally substituted by R^(115a), tetrazolyl, amidino,—CON(R^(115b))R^(115c), —SO₂N(R^(115b))R^(115c), —N(R^(115b))R^(115c),—SO₂R^(115d), —SOR^(115d), —SR^(115d), or C₂-C₆ alkenyl optionallysubstituted by COOR^(115e),

[0060] R^(115a) presents one or two selected from the group consistingof carboxy, morpholino, morpholino-carbonyl, amino, hydroxy, cyano,C₁-C₆ alkoxy carbonyl, carbamoyl optionally substituted by cyano-C₁-C₆alkyl, methylamino-carbonyl, dimethylamino-carbonyl, —NH—SO₂—CH₃,tetrazolyl, dihydrooxazolyl optionally substituted by C₁-C₆ alkyl, and9-10 membered unsaturated condensed ring containing one N atomoptionally substituted by ═O,

[0061] R^(115b) represents H or C₁-C₆ alkyl,

[0062] R^(115c) represents H, amino, C₁-C₆ alkyl amino, di(C₁-C₆alkyl)amino, amidino, morpholino-C₁-C₆ alkyl carbonyl, carboxy-C₁-C₆alkyl carbonyl, or straight- or branched C₁-C₆ alkyl optionallysubstituted by one or two selected from the group consisting of hydroxy,phenyl, morpholino, di(C₁-C₆ alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆alkyl substituted amino, C₁-C₆ alkoxy-carbonyl, and carboxy,

[0063] or R^(115b) and R^(115c) together with the adjacent N form 5 or 6membered saturated hetero cyclic ring optionally having one N or O atomsother than the adjacent N and optionally substituted by C₁-C₆ alkyl,

[0064] R^(115d) represents hydroxy, hydroxy C₁-C₆ alkyl, C₁-C₆ alkyl,hydroxy-carbonyl-C₁-C₆ alkyl, or C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl,

[0065] R^(115e) represents hydrogen or C₁-C₆ alkyl,

[0066] R¹¹⁶ represents H, C₁-C₆ alkoxy, C₁-C₆ alkyl, halogen, orcarbamoyl,

[0067] R¹¹⁷ represents H, halogen, or C₁-C₆ alkoxy,

[0068] R¹¹⁸ represents one to three substituents selected from the groupconsisting of C₁-C₆ alkyl, amino, C₁-C₆ alkoxy, COOR^(118a) (H or C₁-C₆alkyl), and ═O

[0069] R¹² represents C₁-C₆ alkyl, —(CH₂)_(q)—OH, —(CH₂)_(q)—CN (q=0, 1,2, 3, 4, 5, or 6), —CO—C₁-C₆ alkyl, or —C₂-C₆ alkenyl,

[0070] R¹³ is identical to R¹¹,

[0071] or R¹² and R¹³ together with the adjacent N atom form 4-6membered saturated heterocyclic ring which may or may not contain 1heteroatom other than the adjacent N atom selected from the groupconsisting of O, N, and S, the 4-6 membered heterocyclic ring optionallyforms spiro with dioxacyclopentane, or is optionally fused with benzene,and/or is optionally substituted by one or two substituents selectedfrom the group consisting of C₁-C₆ alkyl, C₁-C₆ alkyl carbonyl, hydroxy,hydroxy C₁-C₆ alkyl, carboxyl, C₁-C₆ alkoxy carbonyl, carbamoyl, phenyl,halogen substituted phenyl, C₁-C₆ alkoxy substituted phenyl, C₁-C₆ alkylsubstituted phenyl, nitro phenyl, hydroxy phenyl, C₁-C₆ alkyl carbonylphenyl, C₁-C₆ alkoxy carbonyl phenyl, pyridyl optionally substituted byCF₃, pyrimidyl, C₃₋₇ cycloalkyl, dioxolanyl, piperidino, halogensubstituted phenyl carbonyl, furyl carbonyl, cyano, dimethylamino,benzyl, oxo residue, piperonyl methyl, halogen substituted diphenylmethyl, and trifluorocarbonyl amino,

[0072] Y is CH or N;

[0073] R² is H, C₁-C₆ alkyl, or carbamoyl;

[0074] R³ is thienyl, pyridyl optionally substituted by halogen or C₁-C₆alkoxy, dioxane fused phenyl, dioxacyclopentane fused phenyl, or phenyloptionally substituted by one to three substituents selected from thegroup consisting of halogen, C₁-C₆ alkyl, nitro, amino, hydroxy, C₁-C₆alkylthio, —OR³¹, —OR³², —NR³³R³⁴, and —SO₂R³⁵,

[0075] wherein R³¹ and R³² are identical or different and representnitro, C₁-C₆ alkyl carbonyl, C₁-C₆ alkoxy carbonyl, C₂-C₆ alkenyl,di(C₁-C₆ alkyl) amino carbonyl, C₁-C₆ alkyl amino carbonyl, —SO₂—R³¹¹,or straight- or branched-C₁-C₆ alkyl optionally substituted by R³¹²,cyclo-C₃-C₇ alkyl optionally substituted by R³¹²,

[0076] R³¹¹ represents C₁-C₆ alkyl, amino, di(C₁-C₆ alkyl) amino C₁-C₆alkyl amino, C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl amino, 5-6 memberedsaturated hetero cyclic ring containing up to 2 heteroatoms of N, S,and/or O and optionally substituted by C₁-C₆ alkyl or carboxy,

[0077] R³¹² represents one selected from the group consisting of C₁-C₆alkoxy, halogen, phenyl optionally substituted by C₁-C₆ alkoxy, di(C₁-C₆alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl substituted amino, or5-6 membered saturated hetero cyclic ring containing up to 2 heteroatomsof N, S, and/or O and optionally substituted by C₁-C₆ alkyl, carbamoyl,or di(C₁-C₆ alkyl)amino,

[0078] R³³ represents H or C₁-C₆ alkyl,

[0079] R³⁴ represents carboxy C₁-C₆ alkyl carbonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkyl optionally substituted by R³⁴¹,

[0080] wherein R³⁴¹ represents dimethylamino, C₁-C₆ alkoxy, morpholino,phenyl, C₁-C₆ alkyl substituted piperazino, oxopyrrolidino, orimidazolyl,

[0081] or —N R³³R³⁴ forms morpholino optionally substituted by C₁-C₆alkyl, thiazinano optionally substituted by C₁-C₆ alkyl, piperidinooptionally substituted by C₁-C₆ alkyl, or pyrrolidino optionallysubstituted by C₁-C₆ alkyl,

[0082] R³⁵ represents amino, di(C₁-C₆ alkyl)amino C₁-C₆ alkyl amino,hydroxy C₁-C₆ alkyl amino, C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl amino,morpholino, piperazino optionally substituted by hydroxy C₁-C₆ alkyl orC₁-C₆ alkyl, or piperidino optionally substituted by carboxy,

[0083] or its tautomeric or stereoisomeric form, or its physiologicallyacceptable salt.

[0084] More preferred compounds of Formula (I) are those wherein:

[0085] R¹ represents —OR¹¹, —SR¹¹, or —NHR¹¹,

[0086] R¹¹ represents phenyl optionally substituted by R¹¹⁵, R¹¹⁶,and/or R¹¹⁷, pyridyl optionally substituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷,or 9-10-membered unsaturated condensed ring which optionally contains upto 3 N atoms and optionally substitued by R¹¹⁸,

[0087] R¹¹⁵ represents H, halogen, amino, hydroxy, nitro, cyano,carboxy, C₁-C₆ alkoxycarbonyl, C₁-C₆ alkoxy, C₁-C₆ alkyl carbonyl,morpholino-C₁-C₆ alkyl-oxy, carboxy-C₁-C₆ alkyl-oxy, trihalogensubstituted methyl, trihalogen substituted methoxy, C₁-C₁₀ straight- orbranched-alkyl optionally substituted by R^(115a), or C₃-C₁₀ cyclo-alkyloptionally substituted by R^(115a), tetrazolyl, amidino,—CON(R^(115b))R^(115c), —SO₂N(R^(115b))R^(115c), —N(R^(115b))R^(115c),—SO₂R^(115d), —SOR^(115d), —SR^(115d), or C₂-C₆alkenyl optionallysubstituted by COOR^(115e),

[0088] R^(115a) represents one or two selected from the group consistingof morpholino, morpholino-carbonyl, amino, hydroxy, cyano, C₁-C₆ alkoxycarbonyl, carbamoyl, methylamino-carbonyl, dimethylamino-carbonyl,—NH—SO₂—CH₃, dihydrooxazolyl optionally substituted by C₁-C₆ alkyl, and9-10 membered unsaturated condensed ring containing one N atomoptionally substituted by ═O,

[0089] R^(115b) represents H or C₁-C₆ alkyl,

[0090] R^(115c) represents H, amino, amidino, morpholino-C₁-C₆ alkylcarbonyl, carboxy-C₁-C₆ alkyl carbonyl, or straight- or branched C₁-C₆alkyl optionally substituted by one or two selected from the groupconsisting of hydroxy, phenyl, morpholino, di(C₁-C₆ alkyl) amino, C₁-C₆alkyl and hydroxy C₁-C₆ alkyl substituted amino, C₁-C₆ alkoxy-carbonyl,and carboxy,

[0091] or R^(115b) and R^(115c) together with the adjacent N form 5 or 6membered saturated hetero cyclic ring optionally having one N or O atomsother than the adjacent N and optionally substituted by C₁-C₆ alkyl,

[0092] R^(115d) represents C₁-C₆ alkyl, hydroxy, hydroxy C₁-C₆ alkyl,hydroxy-carbonyl-C₁-C₆ alkyl, or C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl,

[0093] R^(115e) represents hydrogen or C₁-C₆ alkyl,

[0094] R¹¹⁶ represents H, C₁-C₆ alkoxy, C₁-C₆ alkyl, halogen, orcarbamoyl,

[0095] R¹¹⁷ represents H, halogen, or C₁-C₆ alkoxy,

[0096] R¹¹⁸ represents C₁-C₆ alkyl, amino, C₁-C₆ alkoxy, COOR^(118a)(R^(118a) is H or C₁-C₆ alkyl), or ═O (mono or di),

[0097] Y is CH or N;

[0098] R² is H;

[0099] R³ is phenyl optionally substituted by two substituents selectedfrom the group consisting of —OR³¹, —OR³², and —NR³³R³⁴,

[0100] wherein R³¹ and R³² are identical or different and representstraight- or branched-C₁-C₆ alkyl optionally substituted by R³¹²,cyclo-C₃-C₇ alkyl optionally substituted by R³¹²,

[0101] R³¹² represents one selected from the group consisting of C₁-C₆alkoxy, halogen, phenyl optionally substituted by C₁-C₆ alkoxy, di(C₁-C₆alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl substituted amino, or5-6 membered saturated hetero ring containing up to 2 heteroatoms of N,S, and/or O and optionally substituted by C₁-C₆ alkyl, carbamoyl, ordi(C₁-C₆ alkyl)amino

[0102] R³³ represents H, or C₁-C₆ alkyl,

[0103] R³⁴ represents C₁-C₆ alkyl optionally substituted by C₁-C₆alkoxyl, or —N R³³R³⁴ forms morpholino optionally substituted by C₁-C₆alkyl,

[0104] or its tautomeric or stereoisomeric form, or its physiologicallyacceptable salt.

[0105] The most preferable compounds of the present invention are asfollows:

[0106][7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]-(1H-indazol-6-yl)-amine;

[0107]2-[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzamide;

[0108]2-[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-5-methoxy-benzamide;

[0109]2-[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzenesulfonamide;

[0110][7-(3,4-Dimethoxy-phenyl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-(1H-indazol-6-yl)-amide;

[0111]4-Amino-2-[7-(3,4-dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzamide;

[0112](7-(3-methoxy-4-[(2-methoxy-ethyl)-methyl-amino]-phenyl)-imidazo[1,2-c]pyrimidin-5-yl)-(4-methoxy-phenyl)-amine;

[0113][7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]-p-tolyl-amine;

[0114](2-Methanesulfonyl-phenyl)-(7-(3-methoxy-4-[(2-methoxy-ethyl)-methyl-amino]-phenyl)-imidazo[1,2-c]pyrimidin-5-yl)-amine;

[0115]2-[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamide;

[0116]2-[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzamide;

[0117]2-Methanesulfonyl-phenyl)-[7-(3-methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]-amine;

[0118]4-[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-phenol;

[0119][7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]-(4-methoxy-phenyl)-amine;and

[0120]2-[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamide

[0121] or its tautomeric or stereoisomeric form, or its physiologicallyacceptable salt.

[0122] The compound of the formula (I) or salts thereof of the presentinvention can be, but not limited to be, prepared by the methods [A]-[F]below.

[0123] [A] The compound (Ia):

[0124] wherein R² are the same as defined above; i represent 0, 1, or 2;R^(11′) represents C₁-C₆ alkyl; and R³⁰ represents optional substituentson the 1, 2, and/or 3 positions of phenyl including hydrogen, OMe,methyl, halogen, and/or morpholino, or a salt thereof can be obtained,for example, by the following process.

[0125] Compound 1, optionally substituted benzonitrile, is commerciallyavailable or can be synthesized from common chemical reagents byconventional methods.

[0126] Compound 1 can be replaced by thienyl nitrile, optionallysubstituted naphtyl nitrile, optionally substituted pyridyl nitrile,dioxane fused phenyl nitrile, or dioxacyclopentane fused phenyl nitrileto produce the compound different at C-7 position from the formula(IIa).

[0127] Compound 2 may be prepared by reacting the anion of CH₃CN, whichis generated by treating acetonitrile with base e.g., LDA, withCompound 1. The reaction may be carried out in ether solvents, such asdiethylether or THF at −78° C. to room temperature overnight.

[0128] Compound 3 may be prepared by reacting compound 2 with thioureain the presence of base, e.g., sodium alkoxide with heating in alcoholsolvent overnight.

[0129] Compound 4, wherein R^(11′) represents C₁-C₆ alkyl may beprepared by alkylating compound 3. Alkylation may be carried out bytreating compound 3 in an appropriate solvent with alkyl halides, suchas C₂H₅I, CH₃I, C₂H₅Br, and CH₃Br in the presence of base e.g.,inorganic bases such as NaHCO₃ and Na₂CO₃, or organic base such astriethylamine at room temperature for 2 hours to overnight.

[0130] Compound 5 may be prepared by treating compound 4 with 2-5equivalents of halogen acetaldehyde e.g., bromoacetaldehyde, or halogenacetal, e.g., bromoacetal, or equivalents thereof. The reaction may becarried out for example in THF-water with heating for 3 hours toovernight.

[0131] Alternatively, compound 4 can be treated with an alpha-halogensubstituted ketone or equivalent thereof to ultimately produce 2′substituted compound of the formula (I) of the present invention.

[0132] Compound 6 is prepared by oxidizing compound 5 by conventionalmethods.

[0133] [B] The compound of the formula (Ib) below:

[0134] wherein R^(30′) represents optional substituents on the 1,2,and/or 3 positions of phenyl including, but not limited to, SO₂R³⁵(wherein R³⁵ is the same as defined) can be prepared by modifying R³⁰ ofthe formula (Ia) above with the use of common chemical reagents byconventional methods.

[0135] [C] Intermediates for further variation

[0136] The compound (Ia) and (Ib) above can be hydrolyzed to synthesizeintermediate compound 7 below:

[0137] wherein R³⁰ and R^(30′) are the same as defined above.

[0138] The reaction maybe carried out by treating compound (Ia) or (Ib)with an aqueous solution of base of 2-5 equivalents on molar base (forexample NaOH or KOH) in methanol or ethanol with heating for 5-6 hours.

[0139] Compound (IIa):

[0140] (wherein L is a leaving group and may be represents, forinstance, halogen atom e.g., chlorine, bromine or iodine atom; C₆-C₁₀arylsulfonyloxy group e.g., benzenesulfonyloxy, polysulfonyloxy, orp-toluenesulfonyloxy; and C₁-C₄ alkylsulfonyloxy group e.g.,methanesulfonyloxy, and the like.halogen) may be prepared by reactingcompound 7 with an appropriate halogenating reagent (for example POCl₃,PCl₅, SOCl₂ etc.) or corresponding sulfonyl chloride or the like in thepresence of a base.

[0141] [D] A general method of producing the intermediate shown by theformula (IIb) or salts thereof as used in preparing the compound of theformula (I) or salts thereof is mentioned below.

[0142] wherein R³⁰ and L are the same as defined above.

[0143] The compounds of formula (IIb) can be synthesized by thefollowing route;

[0144] Compound 10 can be prepared by reacting 2,4-dichloropyrimidine(Compound 9) with aryl lithium reagent, which is generated in situ bytreating aromatic halogen (for example, Cl, Br, I) with n-butyl lithium.The reaction can be carried out in ether solvents (such as diethyl etheror THF) at −78° C. to 50° C. for 5 to 24 hours. (The aromatic halogensare commercially available or can be synthesized from common chemicalreagents by conventional methods.)

[0145] Compound 11 can be prepared by treating compound 10 withhydrazine hydrate or anhydrous hydrazine in appropriate solvent (forexample, CHCl₃, THF etc.). The reaction can be carried out by treatingcompound 10 with 5-30 equivalents of hydrazine hydrate or anhydroushydrazine in CHCl₃ or THF at 0° C. to 100° C. for 5-24 hours.

[0146] Compound 12 can be prepared by reacting Compound 11 withcarboxylic acid or orth-acid ester. The reaction can be carried outusing carboxylic acid, or orth-acid ester as solvent at 50° C. to 200°C. for 3 to 20 hours.

[0147] Compounds 13 (where L=aryl or alkyl sulfonyloxy) can be preparedby reacting compound 12 with the corresponding sulfonyl chloride in thepresence of a base.

[0148] Compound 13 (where L=halogen) can be prepared by reactingcompound 12 with appropriate halogenating reagent (for example POCl₃,PCl₅, SOCl₂, etc.) in the presence of a base. The reaction may betypically carried out, without limitation, using the halogenatingreagent as the solvent under reflux condition for 3 to 5 hours.

[0149] [E] The compound (Ie):

[0150] wherein R², R³ and Y are the same as defined above and R^(1′)represents —OR¹¹, —NHR¹¹, —SR^(11″), —SO₂R^(11″), —SOR^(11″), or—NR¹²R¹³ (wherein R¹¹, R¹², and R¹³ are the same as defined above;R^(11″) is identical to R¹¹ but C₁-C₆ alkyl) or a salt thereof can beobtained, for example, by reacting a compound shown by the generalformula (II):

[0151] wherein Y, R², R³, and L are the same defined as defined above,

[0152] or a salt thereof, with a compound shown by the general formula(III):

HR^(1′)  (III)

[0153] or a salt thereof.

[0154] This reaction can be carried out without solvent or in a solventincluding, for instance, alcohols such as methanol and ethanol; ethers,such as dioxane, diethyl ether, and tetrahydrofuran (THF); aromatichydrocarbons such as benzene, toluene and xylene; nitriles such asacetonitrile; amides such as dimethylformamide (DMF) anddimethylacetamide; sulfoxides such as dimethyl sulfoxide, and others.

[0155] The amount of the compound shown by the formula (III) or a saltthereof per mole of the compound shown by the formula (II) or the saltthereof as used in the reaction is, usually ⅕ to 5 moles and preferablyabout ½ to 2 moles.

[0156] The reaction temperature can be optionally set depending on thecompounds to be reacted. The reaction temperature is usually, but notlimited to, about 10° C. to 200° C. and preferably about 20° C. to 100°C. The reaction may be conducted for, usually, 30 minutes to 48 hoursand preferably 1 to 24 hours.

[0157] Some reaction can be advantageously conducted in the presence ofa base. Examples of the base include an alkali metal hydride such assodium hydride or potassium hydride; alkali metal alkoxide such assodium methoxide or sodium ethoxide; alkali metal hydroxide such assodium hydroxide or potassium hydroxide; carbonates such as sodiumcarbonate or potassium carbonate, and hydrogen carbonates such as sodiumhydrogen carbonate and potassium hydrogen carbonate; organic amines suchas triethylamine.

[0158] [F] Alternatively, the compound of the formula (If) below:

[0159] wherein R², R³, R¹¹, R¹⁴ and R¹⁵ are the same as defined above,can be prepared by reacting a compound shown by a compound of theformula (II) with Grignard reagent or according to the knownconventional methods.

[0160] When the compound shown by the formula (I) or a salt thereof hastautomeric isomers and/or stereoisomers (e.g, geometrical isomers andconformational isomers), each of their separated isomer and mixtures arealso included in the scope of the present invention.

[0161] When the compound shown by the formula (I) or a salt thereof hasan asymmetric carbon in the structure, their optically active compoundsand racemic mixtures are also included in the scope of the presentinvention.

[0162] Typical salts of the compound shown by the formula (I) includesalts prepared by reaction of the compounds of the present inventionwith a mineral or organic acid, or an organic or inorganic base. Suchsalts are known as acid addition and base addition salts, respectively.

[0163] Acids to form acid addition salts include inorganic acids suchas, without limitation, sulfuric acid, phosphoric acid, hydrochloricacid, hydrobromic acid, hydriodic acid and the like, and organic acids,such as, without limitation, p-toluenesulfonic acid, methanesulfonicacid, oxalic acid, p-bromophenylsulfonic acid, carbonic acid, succinicacid, citric acid, benzoic acid, acetic acid, and the like.

[0164] Base addition salts include those derived from inorganic bases,such as, without limitation, ammonium hydroxide, alkaline metalhydroxide, alkaline earth metal hydroxides, carbonates, bicarbonates,and the like, and organic bases, such as, without limitation,ethanolamine, triethylamine, tris(hydroxymethyl)aminomethane, and thelike. Examples of inorganic bases include, sodium hydroxide, potassiumhydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate,potassium bicarbonate, calcium hydroxide, calcium carbonate, and thelike.

[0165] The compound of the present invention or a salts thereof,depending on its substituents, may be modified to form lower alkylestersor known other esters; and/or hydrates or other salvates. Those esters,hydrates, and salvates are included in the scope of the presentinvention.

[0166] The compound of the present invention may be administered in oralforms, such as, without limitation normal and enteric coated tablets,capsules, pills, powders, granules, elixirs, tinctures, solution,suspensions, syrups, solid and liquid aerosols and emulsions. They mayalso be administered in parenteral forms, such as, without limitation,intravenous, intraperitoneal, subcutaneous, intramuscular, and the likeforms, well-known to those of ordinary skill in the pharmaceutical arts.The compounds of the present invention can be administered in intranasalform via topical use of suitable intranasal vehicles, or via transdermalroutes, using transdermal delivery systems well-known to those ofordinary skilled in the art.

[0167] The dosage regimen with the use of the compounds of the presentinvention is selected by one of ordinary skill in the arts, in view of avariety of factors, including, without limitation, age, weight, sex, andmedical condition of the recipient, the severity of the condition to betreated, the route of administration, the level of metabolic andexcretory function of the recipient, the dosage form employed, theparticular compound and salt thereof employed.

[0168] The compounds of the present invention are preferably formulatedprior to administration together with one or morepharmaceutically-acceptable excipients. Excipients are inert substancessuch as, without limitation carriers, diluents, flavoring agents,sweeteners, lubricants, solubilizers, suspending agents, binders, tabletdisintegrating agents and encapsulating material.

[0169] Yet another embodiment of the present invention is pharmaceuticalformulation comprising a compound of the invention and one or morepharmaceutically-acceptable excipients that are compatible with theother ingredients of the formulation and not deleterious to therecipient thereof. Pharmaceutical formulations of the invention areprepared by combining a therapeutically effective amount of thecompounds of the invention together with one or morepharmaceutically-acceptable excipients therefor. In making thecompositions of the present invention, the active ingredient may bemixed with a diluent, or enclosed within a carrier, which may be in theform of a capsule, sachet, paper, or other container. The carrier mayserve as a diluent, which may be solid, semi-solid, or liquid materialwhich acts as a vehicle, or can be in the form of tablets, pillspowders, lozenges, elixirs, suspensions, emulsions, solutions, syrups,aerosols, ointments, containing, for example, up to 10% by weight of theactive compound, soft and hard gelatin capsules, suppositories, sterileinjectable solutions and sterile packaged powders.

[0170] For oral administration, the active ingredient may be combinedwith an oral, and non-toxic, pharmaceutically-acceptable carrier, suchas, without limitation, lactose, starch, sucrose, glucose, sodiumcarbonate, mannitol, sorbitol, calcium carbonate, calcium phosphate,calcium sulfate, methyl cellulose, and the like; together with,optionally, disintegrating agents, such as, without limitation, maize,starch, methyl cellulose, agar bentonite, xanthan gum, alginic acid, andthe like; and optionally, binding agents, for example, withoutlimitation, gelatin, acacia, natural sugars, beta-lactose, cornsweeteners, natural and synthetic gums, acacia, tragacanth, sodiumalginate, carboxymethylcellulose, polyethylene glycol, waxes, and thelike; and, optionally, lubricating agents, for example, withoutlimitation, magnesium stearate, sodium stearate, stearic acid, sodiumoleate, sodium benzoate, sodium acetate, sodium chloride, talc, and thelike.

[0171] In powder forms, the carrier may be a finely devided solid whichis in admixture with the finely divided active ingredient. The activeingredient may be mixed with a carrier having binding properties insuitable proportions and compacted in the shape and size desired toproduce tablets. The powders and tablets preferably contain from about 1to about 99 weight percent of the active ingredient which is the novelcomposition of the present invention. Suitable solid carriers aremagnesium carboxymethyl cellulose, low melting waxes, and cocoa butter.

[0172] Sterile liquid formulations include suspensions, emulsions,syrups and elixirs. The active ingredient can be dissolved or suspendedin a pharmaceutically acceptable carrier, such as sterile water, sterileorganic solvent, or a mixture of both sterile water and sterile organicsolvent.

[0173] The active ingredient can also be dissolved in a suitable organicsolvent, for example, aqueous propylene glycol. Other compositions canbe made by dispersing the finely divided active ingredient in aqueousstarch or sodium carboxymethyl cellulose solution or in a suitable oil.

[0174] The formulation may be in unit dosage form, which is a physicallydiscrete unit containing a unit dose, suitable for administration inhuman or other mammals. A unit dosage form can be a capsule or tablets,or a number of capsules or tablets. A “unit dose” is a predeterminedquantity of the active compound of the present invention, calculated toproduce the desired therapeutic effect, in association with one or moreexcipients. The quantity of active ingredient in a unit dose may bevaried or adjusted from about 0.1 to about 1000 milligrams or moreaccording to the particular treatment involved.

[0175] Typical oral dosages of the present invention, when used for theindicated effects, will range from about 0.01 mg/kg/day to about 100mg/kg/day, preferably from 0.1 mg/kg/day to 30 mg/kg/day, and mostpreferably from about 0.5 mg/kg/day to about 10 mg/kg/day. In the caseof parenteral administration, it has generally proven advantageous toadminister quantities of about 0.001 to 100 mg/kg/day, preferably from0.01 mg/kg/day to 1 mg/kg/day. The compounds of the present inventionmay be administered in a single daily dose, or the total daily dose maybe administered in divided doses, two, three, or more times per day.Where delivery is via transdermal forms, of course, administration iscontinuous.

[0176] The effect of the present compounds were examined by thefollowing assays and pharmacological tests.

[0177] [Syk Tyrosine Kinase Inhibitory Assay]

[0178] (1) Preparation of Syk Protein

[0179] A cDNA fragment encoding human Syk openreading frame was clonedfrom total RNA of human Burkitt's lymphoma B cell lines, Raji (AmericanType Culture Collection), with the use of RT-PCR method. The cDNAfragment was inserted into pAcG2T (Pharmingen, San Diego, Calif.) toconstruct a baculovirus transfer vector. Then the vector, together withthe linearized baculovirus (BaculoGold™, Pharmingen), was used totransfect Sf21 cells (Invitrogen, San Diego, Calif.).

[0180] Generated recombinant baculovirus was cloned and amplified inSf21 cells. Sf21 cells were infected with this amplified high titervirus to produce a chimeric protein of Syk kinase fused byglutathione-S-transferase (GST).

[0181] The resulting GST-Syk was purified with the use of glutathionecolumn (Amersham Pharmacia Biotech AB, Uppsala, Sweden) according to themanufacturer's instruction. The purity of the protein was confirmed tobe more than 90% by SDS-PAGE.

[0182] (2) Synthesize of a Peptide

[0183] Next, a peptide fragment of 30 residues including two tyrosineresidues, KISDFGLSKALRADENYYKAQTHGKWPVKW, was synthesized by a peptidesynthesizer. The N-terminal of the fragment was then biotinylated toobtain biotinylated activation loop peptide (AL).

[0184] (3) The Measurement of Syk Tyrosine Kinase Activity

[0185] All reagents were diluted with the Syk kinase assay buffer (50 mMTris-HCl (pH 8.0), 10 mM MgCl₂, 0.1 mM Na₃VO₄, 0.1% BSA, 1 mM DTT).First, a mixture (35 μl) including 3.2 μg of GST-Syk and 0.5 μg of ALwas put in each well in 96-well plates. Then 5 μl of a test compound inthe presence of 2.5% dimethylsulfoxide (DMSO) was added to each well. Tothis mixture was added 300 μM ATP (10 μl) to initiate the kinasereaction. The final reaction mixture (50 μl) consists of 0.65 nMGST-Syk, 3 μM AL, 30 μM ATP, a test compound, 0.25% DMSO, and a Sykkinase assay buffer.

[0186] The mixture was incubated for 1 hr at room temperature, and thereaction was terminated by the addition of 120 μl of termination buffer(50 mM Tris-HCl (pH 8.0), 10 mMEDTA, 500 mM NaCl, 0.1% BSA). The mixturewas transferred to streptavidin-coated plates and incubated for 30 minat room temperature to combine biotin-AL to the plates. After washingthe plates with Tris-buffered saline (TBS) (50 mM Tris-HCl (pH 8.0), 138mM NaCl, 2.7 mM KCl) containing 0.05% Tween-20 for 3 times, 100 μl ofantibody solution consisting of 50 mM Tris-HCl (pH 8.0), 138 mM NaCl,2.7 mM KCl, 1% BSA, 60 ng/ml anti-phosphotyrosine monoclonal antibody,4G10 (Upstate Biotechnology), which is labeled with europium by AmershamPharmacia's kit in advance, was added and incubated at room temperaturefor 60 min. After washing, 100 μl of enhancement solution (Amershampharmacia Biotech) was added and then time-resolved fluorescence wasmeasured by multi-label counter ARVO (Wallac Oy, Finland) at 340nm forexcitation and 615 nm for emission with 400 msec of delay and 400 msecof window.

[0187] [Src Kinase Inhibitory Assay]

[0188] (1) Preparation of Src and its Substrate

[0189] Human Src kinase was purchased from Upstate Biotechnology (LakePlacid, N.Y.).

[0190] The CDNA fragment encoding T cell receptor zeta-chain (Zeta) wasobtained from a Jurkat cDNA library. Then Zeta was expressed as a fusionprotein with poly histidine-tag (His-Zeta) in E. coli and purified bynickel resign as described in the instruction of His-tag purificationkit (Novagen, Madison, Wis.).

[0191] His-Zeta was diluted with TBS to prepare solution with theconcentration of 10 μg/ml. The resulting solution (100 μl) was put in aneach well of a nickel plate. Plates were incubated for overnight at 4°C. to coat the surface of the well with His-Zeta.

[0192] After washing the plate with 0.05% Tween-20 containing TBS for 3times, 35 μl of reaction mixture containing 0.1 ng Src was put into aneach well of a His-Zeta coated nickel plate. Then, 5 μl of a testcompound in the presence of 2.5% DMSO was added to each well. To thismixture was added 10 μl of 100 μM ATP to initiate the kinase reaction.Final mixture consists of 0.1 ng Src, a test compound, 0.25% DMSO, 10 μMATP in the Src kinase assay buffer (50 mM Hepes (pH 7.4.), 10 mM MgCl₂,0.125% BSA). The mixture was incubated for 45 min at RT with gentleshaking, and the reaction was terminated by washing the wells. To detectthe phosphorylation of His-Zeta, 100 μl of antibody solution witheuropium-labeled 4G10 was added and time-resolved fluorescence wasmeasured as mentioned above.

[0193] [The Measurement of Hexosaminidase Release from RBL-2H3 Cells]

[0194] RBL-2H3 cells were maintained in minimum essential mediumsupplemented by 15% FCS, penicillin G sodium (100 units/ml), andstreptomycin sulfate (100 units/ml). Thirty two thousand (3.2×10⁴) cellswere seeded in each well of 96 well plate and cultured for more than 24hr in the presence of 0.3 μg/ml of anti-dinitrophenol (DNP) monoclonalmouse IgE (SPE-7: Sigma-Aldrich Corp., St. Louis, Mo.). After the gentlewashing of the wells with PIPES buffer (25 mM PIPES, 125 mM NaCl, 2.7 mMKCl, 5.6 mM glucose, 1 mM CaCl₂, 0.1% BSA, pH 7.4), cells were treatedwith a test compound (45 μl) in the presence of 0.3% DMSO for 15 min at37° C. and then stimulated with 5 μl of DNP-conjugated bovine serumalbumin (DNP-BSA, Sigma-Aldrich) with the concentration of 0.1 μg/ml forfurther 45 min at 37° C. The supernatant (20 μl) was recovered andincubated with equal volume of 1 mM p-nitrophenyl-β-D-glucosaminidase in0.1 M sodium citrate (pH 4.5) for 1 hr at 37° C. to detect the amount ofreleased hexosaminidase. The reaction of hexosaminidase was terminatedby the addition of 200 μl of 0.1 M Na₂CO₃/0.1 M NaHCO₃ (pH 10) and theabsorbance at OD₄₁₀ was measured to determine the amount of release ofhexosaminidase.

[0195] [Passive Cutaneous Anaphylaxis (PCA) Test in Rats]

[0196] 6 Weeks old male Wistar rats were sensitized intradermally (i.d.)on their shaved backs with 50 μl of 0.1 μg/ml mouse anti-DNP IgEmonoclonal antibody (SPE-7) under a light anesthesia. After 24 hours,the rats were challenged intravenously with 1 ml of saline containing0.6 mg DNP-BSA (30) (LSL CO., LTD) and 0.005 g of Evans blue. Compoundswere injected intraperitoneally (i.p.) 0.5 hr prior to antigeninjection. Rats without the sensitization, challenge, and compoundtreatment were used for a blank (control) and rats with sensitization,challenge and vehicle treatment were used to determine a value withoutinhibition. Thirty min after the challenge, the rats were killed, andthe skin of the back was removed. Evans blue dye in the skin wasextracted in formamide overnight at 63° C. Then an absorbance at 620 nmwas measured to obtain the optical density of the leaked dye.

[0197] Percent inhibition of PCA with a compound was calculated asfollows:

% inhibition={(mean vehicle value−sample value)/(mean vehicle value−meancontrol value)}×100

[0198] [Anaphylactic Bronchoconstriction in Rats]

[0199] 6 Weeks old male Wistar rats were sensitized intravenously (i v.)with 10 μg mouse anti-DNP IgE, SPE-7, and 1 days later, the rats werechallenged intravenously with 0.3 ml of saline containing 1.5 mg DNP-BSA(30) under anesthesia with urethan (1000 mg/kg, i.p.) and gallamine (50mg/kg, i.v.). The trachea was cannulated for artifical respiration (2ml/stroke, 70 strokes/min). Pulmonary inflation pressure (PIP) wasrecorded thruogh a side-arm of cannula connected to pressure transducer.Change in PIP reflect change of both resistance and compliance of thelungs. To evaluate the drugs, each drug was given i.v. 5 min beforechallenge.

[0200] In vitro test results are shown in the tables of the Examplesbelow. The data corresponds to the compounds as yielded by solid phasesynthesis and thus to levels of purity of about 40 to 90%. For practicalreasons, the compounds are grouped in four classes of activity asfollows:

IC ₅₀ =A≦0.5 μM<B≦2 μM<C≦10 μM<D

[0201] The compounds of the present invention also show excellentselectivity, and strong activity in vivo assays.

EXAMPLES

[0202] The present invention will be described in detail below in theform of examples, but they should by no means be construed as definingthe metes and bounds of the present invention.

[0203] In the examples below, all quantitative data, if not statedotherwise, relate to percentages by weight. The mass determinations werecarried out by MAT95 (Finnigan MAT).

Example 1

[0204]

[0205] To a solution of diisopropylamine (52.7 g, 521 mmol) in THF (1 L)at −78° C. was added n-BuLi (1.6 M in hexane, 272 ml, 435 mmol) over 15min. Acetonitrile (18.8 g, 460 mmol) in THF (200 m) was added to the LDA(Lithium diisopropylamide) solution over 15 min. to create a whiteprecipitate. The resulting mixture was stirred for 30 min at −78° C. andwas then treated with a solution of 3,4-dimethoxybenzonitrile (50 g, 306mmol) in THF (200 ml). The resulting mixture was stirred at −78° C. for20 min., and then allowed to slowly warm to room temperature to afford aclear orange solution. The solution was stirred at room temperatureovernight. Water (300 ml) was added to the reaction mixture. Thesolution was partially concentrated under reduced pressure, and thenseparated between water and CH₂Cl₂. The organic phase was washed withbrine and dried over Na₂SO₄. Concentrated under reduced pressure to givethe crude product which was purified by recrystalization from MeOH. Twocrops were obtained. (total 50.0 g, 80% yield)

[0206] To a solution of sodium ethoxide in ethanol [prepared from sodium(11.3 g, 490 mmol) and ethanol (240 ml)] was added thiourea (28.0 g, 367mmol) and alpha cinnamonitrile (50 g, 245 mmol). The resulting mixturewas heated under reflux overnight. The mixture was cooled to roomtemperature and diluted with water (300 ml), and then neutralized with1N HCl. The resulting precipitate was filtered and washed with water andthen THF. (64 g, quant.)

[0207] To a solution of iodoethane (75.6 g, 485 mmol) and4-amino-6-(3,4-dimethoxyphenyl)-2-mercapto-pyrimidine (63.8 g, 242 mmol)in DMSO (560 ml) was added a saturated aqueous NaHCO₃ solution (270 ml).The reaction mixture was stirred at room temperature overnight. Themixture was diluted with water (400 ml) and the precipitate was filteredto give the desired product. (51.3 g, 73%)

[0208] A solution of4-amino-6-(3,4-dimethoxyphenyl)-2-(ethylthio)pyrimidine (25.7 g, 880mmol) and bromoacetaldehyde dimethyl acetal (29.8 g, 1760 mmol) in water(500 ml) and THF (35 ml) was heated under reflux overnight. The mixturewas cooled to room temperature. The precipitate was filtered and washedwith water and MeOH. The product was isolated as the HBr salt and wasused for the next reaction without neutralization. (25.0 g, 78%,Molecular weight: 315.3968)

[0209] With the use of other commercially available benzonitriles assubstitutes for the 3,4-dimethoxybenzonitrile, and according to theprocedure that is similar to that described above, following compoundsshown in Table 1 below were prepared. IC₅₀ classes defined above arelisted in the tables. TABLE 1 Ex. Activity No. MOLSTRUCTURE MOLWEIGHTgrade MS NMR 1-1

373.4338 B 374 .(DMSO d-6) 1.52 (3H, t, J = 7.1 Hz), 3.53 (2H, q, J =7.1 Hz), 3.82 (3H, s), 3.86 (3H, s), 3.88 (3H, s), 7.10 (1H, d, J = 8.7Hz), 7.78-7.83 (2H, m), 8.00 (1H, s), 8.27 (1H, s) 1-2

286.3579 C 287 (DMSO d-6) 1.49 (3H, t, J = 7.2 Hz), 3.52 (2H, q, J = 7.2Hz), 3.93 (3H, s), 6.95 (1H, d, J = 8.7 Hz), 7.71 (1H, d, J = 1.1 Hz),7.83 (1H, s), 8.01 (1H, s), 8.47 (1H, dd), 9.03 (1H, d, J = 2.3 Hz) 1-3

299.3538 B (CDCl₃) d 1.57 (3H, 1, J = 7.3 Hz), 3.51 (2H, q, J = 7.3 Hz),6.04 (2H, s), 6.91 (1 H, d, J = 8.1 Hz), 7.47 (1H, d, J = 0.6 Hz),7.56-7.6 (4H, m). 1-4

301.3697 ND 1-5

285.3703 B 286 1-6

335.4308 C 1-7

387.4609 388 (DMSO-d6) 1.34 (3H, t, J = 7.1 Hz), 1.52 (3H, t, J = 7.2Hz), 3.53 (2H, q, J = 7.2 Hz), 3.83 (3H, s), 3.88 (3H, s), 4.34 (2H, q,J = 7.1 Hz), 7.09 (1H, d, J = 8.4 Hz), 7.76-7.82 (2H, m), 7.99 (1H, s),8.23 (1H, s) 1-8

329.4239 A 330 (DMSO-d6) 1.50 (3H, t, J = 7.2 Hz), 2.36 (3H, s), 3.50(2H, q, J = 7.2 Hz), 3.82 (3H, s), 3.87 (3H, s), 7.07 (1H, d, J = 9.0Hz), 7.52 (1H, s), 7.52 (1H, s), 7.76-7.79 (2H, m), 7.84 (1H, s) 1-9

315.3968 316 (DMSO-d6) 1.47 (3H, t, J = 7.2 Hz), 3.47 (2H, q, J = 7.3Hz), 3.85 (3H, s), 3.94 (3H, s), 6.69-6.73 (2H, m), 7.67 (1H, d, J = 1.4Hz), 7.77 (1H, s), 7.92 (1H, s), 8.13 (1H, dd) 1-10

339.3416 340 (DMSO-d6) 1.50 (3H, t, J = 7.3 Hz), 3.53 (2H, q, J = 7.3Hz), 7.50 (1H, d, J = 8.1 Hz), 7.75 (1H, s), 7.86 (1H, s), 8.08 (1H, s),8.31—8.36 (2H, m) 1-11

269.3709 (DMSO-d6) 1.50 (3H, t, J = 7.3 Hz), 2.37 (3H, s), 3.52 (2H, q,J = 7.3 Hz), 7.32 (2H, d, J = 8.1 Hz), 7.70 (1H, s), 7.81 (1H, s), 7.95(1H, s), 8.10 (2H, d, J = 8.2 Hz) 1-12

301.4349 B 302 (DMSO-d6) 1.50 (3H, t, J = 7.3 Hz), 2.54 (3H, s), 3.52(2H, q, J = 7.2 Hz), 7.38 (2H, d, J = 8.6 Hz), 7.71 (1H, d), 7.81 (1H,s), 7.98 (1H, s), 8.13-8.17 (2h, m) 1-13

313.3795 B 314 (CDCl3) d 1.56 (3H, t, J = 7.3 Hz), 3.51 (2H, q, J = 7.3Hz), 4.32 (3H, s), 6.96 (1H, d, J = 8.5 Hz), 7.46 (1H, d, J = 0.6 Hz),7.56 (1H, dd, J =2.2, 8.6 Hz), 7.62 (3H, m). 1-14

269.3709 1-15

255.3438 1-16

271.278

Example 2

[0210] With the use of 3-methoxybenzonitrile, and according to thesimilar procedure to that of Example 1,5-Ethylsulfanyl-7-(3-methoxyphenyl)-imidazo[1,2-c])pyrimidine wasprepared.

[0211] Then to 5 ml of chlorosulfonic acid was added5-Ethylsulfanyl-7-(3-methoxyphenyl)-imidazo[1,2-c])pyrimidine (200 mg,0.70 mmol). The mixture was stirred at room temperature overnight. Thereaction mixture was added slowly to ice water. Extraction was carriedout with CH₂Cl₂. The organic layer was washed with brine and dried overMgSO₄. The organic layer was then concentrated to give4-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7yl)-2-methoxy-benzenesulfonylchloride(201 mg, 75%).

[0212] A solution of4-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7yl)-2-methoxy-benzenesulfonylchloride(200 mg, 0.52 mmol) and piperidine (89 mg, 1.04 mmol) in CH₂Cl₂: MeOH(2:1, 5 ml). was stirred overnight at room temperature. Water was addedto the reaction mixture and extraction was carried out with CH₂Cl₂. Thecombined organic layer was washed with brine and dried over Na₂SO₄. Theorganic layer was concentrated to give the crude product of5-Ethylsulfanyl-7-[3-methoxy-4-(piperidine-1-sulfonyl)-phenyl]imidazo[1,2-c]pyrimidinewhich was purified by preparative thin layer chromatography (45 mg,20%).

[0213] Molecular weight: 432.5667

[0214] Activity grade: C-D

[0215]¹H-NMR (DMSO d-6) 1.21-1.40 (6H, m), 1.39 (3H, t, J=7.2 Hz),2.80-2.83 (4H, m), 3.37 (2H, q, J=7.2 Hz), 3.88 (3H, s), 7.13 (1H, d,J=2.6 Hz), 7.21 (1H, dd), 7.50 (1H, s), 7.75 (1H, d, J=1.1 Hz),7.88-7.91 (2H, m)

[0216] According to the procedure that is similar to that describedabove, following compounds shown in Table 2 below were prepared. IC₅₀classes defined above are listed in the tables. TABLE 2 2-1

461.609 B 462 (DMSO-d6) 1.51 (3H, t, J = 7.2 Hz), 2.38 (2H, 1, J = 6.1Hz), 2.63 (3H, s), 3.08-3.11 (4H, m), 3.41-3.58 (4H, m), 7.59 (1H, d, J= 8.1 Hz), 7.75 (1H, s), 7.87 (1H, s), 8.12 (1H, s), 8.37 (1H, dd), 8.61(1H, s) 2-2

408.5013 A 409 (DMSO-d6) 1.51 (3H, t, J = 7.2 Hz), 2.80-2.91 (2H, m),3.38 (2H, q, J = 6.3 Hz), 3.52 (2H, q, J = 7.2 Hz), 3.98 (3H, s), 4.64(1H, t, J = 5.6 Hz), 7.17 (1H, br), 7.36 (1H, d, J = 8.8 Hz), 7.72 (1H,d, J = 1.4 Hz), 7.84 (1H, s), 7.99 (1H, s), 8.42 (1H, dd) 2-3

477.6084 A 478 (DMSO-d6) 1.51 (3H, t, J = 7.2 Hz), 2.38 (2H, t, J = 6.2Hz), 2.43-2.51 (4H, m), 3.11-3.16 (4H, m), 3.42-3.54 (4H, m), 3.97 (3H,s); 4.35(1H, t, J = 5.4 Hz), 7.39 (1H, d, J = 8.9 Hz), 7.72 (1H, d, J =1.4 Hz), 7.84 (1H, s), 8.01 (1H, s), 8.42-8.47 (1H, dd), 8.61 (1H, d, J= 2.4 Hz) 2-4

493.6731 B 494 (DMSO-d6) 1.49 (3H, t, J = 7.2 Hz), 2.40 (2H, t, J = 6.0Hz), 2.48-2.54 (4H, m), 3.25-3.30 (4H, m), 3.42-3.54 (4H, m), 4.34 (1H,t, J = 5.4 Hz), 7.76 (1H, d, J = 1.3 Hz), 7.88-7.91 (2H, m), 8.16 (1H,s), 8.48-8.52 (1H, dd), 8.69 (1H, d, J = 1.8 Hz) 2-5

392.502 A 393 (DMSO-d6) 1.51 (3H, t, J = 7.2 Hz), 2.63 (3H, s), 2.92(2H, q, J =5.9 Hz), 3.40 (2H, q, J = 5.8 Hz), 3.54 (2H, q, J = 7.2 Hz),4.69 (1H, t, J = 5.6 Hz), 7.53 (1H, d, J = 8.0 Hz), 7.74-7.79 (2H, m),7.87 (1H, s), 8.07 (1H, s), 8.29-8.33 (1H, m), 8.67 (1H, s) 2-6

434.5388 C-D 435 (DMSO d-6) 1.39 (3H, t, J = 7.2 Hz), 2.79-2.82 (4H, m),3.26-3.41 (6H, m), 3.89 (3H, s), 7.15 (1H, d, J = 2.6 Hz), 7.23 (1H,dd), 7.52 (1H, s), 7.75 (1H, d, J = 1.1 Hz), 7.88-7.92 (2H, m) 2-7

364.4484 C-D 365 (DMSO d-6) 1.38 (3H, t, J = 7.1 Hz), 3.39 (2H: q, J =72 Hz), 3.87 (3H, s), (3H, m), 7.59 (1H, s), 7.75 (1H, d, J =1.1 Hz),7.87 (1H, s), 8.00 (1H, d, J =8.7 Hz) 2-8

435.5705 C-D 436 (DMSO d-6) 1.39 (3H, t, J = 7.4 Hz), 2.05 (6H), 2.26(2H, t, J = 6.8 Hz), 2.80 (2H, t, J = 6.8 Hz), 3.88 (3H, s), 7.13-19(3H, m), 7.56 (1H, s), 7.76 (1H, s), 7.94 (1H, d, J = 8.7 Hz) 2-9

447.5815 C-D 448 (DMSO d-6) 1.40 (3H, t, J = 7.2 Hz), 2.78-2.81 (4H, m),3.89 (3H, s), 7.16 (1H, d, J = 2.6 Hz), 7.22 (1H, dd), 7.52 (1H, s),7.76 (1H, d , J = 1.1 Hz), 7.88-7.94 (2H, m) 2-10

476.5756 C-D 477 (DMSO d-6) 1.39 (3H, t, J = 7.2 Hz), 3.85 (3H, s), 7.14(1H, d, J = 2.6 Hz), 7.21 (1H, dd), 7.49 (1H, s), 7.78 (1H, s),7.88-7.94 (2H, m), 12.32 (1H, br) 2-11

464.5646 C-D 465 (DMSO d-6) 1.13 (3H, t, J = 7.2 Hz), 1.38 (3H, t, J=7.2 Hz), 2.36 (2H, t, J = 6.8 Hz), 2.75-2.95 (2H, m), 3.38 (2H, q, J=7.2 Hz), 3.89 (3H, s), 4.00 (2H, q, J = 7.1 Hz), 7.11 (1H, d, J =2.6Hz), 7.19 (1H, dd), 7.33 (1H, br), 7.52 (1H, s), 7.75 (1H, d, J = 1.5Hz), 7.86-7.94 (2H, m)

Example 3

[0217] To 4-hydroxy-3-methoxybenzonitrile (20.0 g, 134 mmol) in acetone(200 ml) were added K₂CO₃ (55.6 g, 402 mmol) and benzyl chloride (23.2ml, 201 mmol). The resulting reaction mixture was refluxed overnight.After cooling to room temperature, acetone was removed by evaporationunder reduced pressure and the residue was recrystallized to obtain4-benzyloxy-3-methoxy-benzonitrile(28.5 g, 88%). Then, according to thesimilar procedure of Example 1,7-(4-Benzyloxy-3-methoxy-phenyl)-5-ethylsulfanyl-imidazo[1,2-c]pyrimidinewas prepared.

[0218] Next, to7-(4-Benzyloxy-3-methoxy-phenyl)-5-ethylsulfanyl-imidazo[1,2-c]pyrimidine(5.0 g, 12.77 mmol) were added TFA (5 ml) and thioanisole (2 ml). Theresulting reaction mixture was stirred at room temperature overnight.Ice water was added and the resulting precipitate was collected byfiltration. The crude product of4-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7-yl)-2-methoxyphenol wassuspended in CH₂Cl₂ and used in the next reaction without furtherpurification. (3.4 g, 88%)

[0219] To4-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7-yl)-2-methoxy-phenol (45mg, 0.15 mmol) in DMF (1 ml) were added bromoethyl ethyl ether (34?l,0.30 mmol) and K₂CO₃ (62 mg, 0.45 mmol). The reaction mixture wasstirred at 50° C. overnight. After cooling to room temperature, themixture was poured into water and extracted with EtOAc. The combinedorganic extract was dried over MgSO₄, concentrated in vacuo and purifiedby preparative thin layer chromatography to give the desired product.(24.6 mg, 43.5%)

[0220] Molecular weight: 373.4774

[0221] Mass spectrometry: 374

[0222] Activity grade: A

[0223]¹H-NMR: (CDCl3) d 1.25 (3H, t, J=7.0 Hz), 1.59 (3H, t, J=7.3 Hz),3.51 (2H, q, J=7.3 Hz), 3.62 (2H, q, J=7.0 Hz), 3.86 (2H, t, J=5.2 Hz),3.96 (3H, s), 4.25 (2H, t, J=5.2 Hz), 7.02 (1H, d, J=8.4 Hz), 7.47 (1H,t, J=0.6 Hz), 7.65 (4H, m).

[0224] According to the procedure that is similar to that of Example 3,following compounds shown in Table 3 below were prepared. IC₅₀ classesdefined above are listed in the tables. TABLE 3 Activity Ex. No.MOLSTRUCTURE MOLWEIGH grade MS NMR 3-1

329.42 A 3-2

341.4351 A 3-3

421.5221 B 422 (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 3.50 (2H, q, J = 7.3Hz), 3.81 (3H, s), 3.98 (3H, s), 5.15 (2H, s), 6.87-6.93 (2H, m), 6.99(1H, d, J = 8.5 Hz), 7.29 (1H, d, J = 8.6 Hz), 7.39 (1H, d, J = 8.6 Hz),7.47 (s, 1H), 7.57-7.69 (m, 4H). material for Exam- ple 3

301.3697 A 302 (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 3.51 (2H, q, J = 7.3Hz), 3.99 (3H, s), 5.81 (1H, s), 7.02 (1H, d, J =8.9 Hz), 7.47 (1H, s),7.62 (4H, m). 3-4

399.5157 A 400 (CDCl3) d 1.37-1.70 (4H, m), 1.59 (3H, t, J = 7.3 Hz),1.73-1.82 (1H, m), 1.87-1.97 (1H, m), 3.48-3.57 (3H, m), 3.81 (1H, m),3.95 (3H, s), 3.96-4.15 (3H, m), 7.00 (1H, d, J =8.4 Hz), 7.47 (1H, t, J= 0.6 Hz), 7.64 (4H, m). 3-5

343.451 A 344 (CDCl3) d 1.43 (6H, d, J 6.0 Hz), 1.59 (3H, t, J = 7.3Hz), 3.51 (2H, q, J = 7.3 Hz), 3.81 (1H, m), 3.95 (3H, s), 7.01 (1 H, d,J = 8.2 Hz), 7.47 (1H, t, J = 0.6 Hz), 7.62 (4H, m). 3-6

383.5163 B 384 (CDCl3) d 1.35 (4H, m), 1.62 (7H, m), 1.85 (2H, m), 2.07(2H, m), 3.50 (2H, q, J = 7.3 Hz), 3.95 (3H, s), 5.15 (2H, s), 4.29 (1H,m), 7.00 (1H, d, J 8.4 Hz), 7.47 (1H, s), 7.64 (4H, m). 3-7

343.4073 A 344 (CDCl3) d 1.58 (3H, t, J = 7.3 Hz), 2.35 (3H, s), 3.51(2H, q, J = 7.3 Hz), 3.94 (3H, s), 7.14 (1H, d, J =8.4 Hz), 7.50 (1H, t,J = 0.7 Hz), 7.69 (4H, m). 3-8

371.4615 B 372 (CDCl3) d 1.35 (6H, d, J = 7.0 Hz), 1.59 (3H, t, J = 7.3Hz), 2.89 (1H, quint, J = 7.0 Hz), 3.50 (2H, q, J =7.3 Hz), 3.92 (3H,s), 7.12 (1H, d, J =8.3 Hz), 7.50 (1H, t, J = 0.7 Hz), 7.62-7.74 (4H,m). 3-9

372.4491 B 373 (CDCl3) d 1.24 (3H, t, J = 7.1 Hz), 1.58 (3H, t, J = 7.3Hz), 3.35 (2H, quint, J = 6.6 Hz), 3.50 (2H, q, J =7.3 Hz), 3.95 (3H,s), 5.06 (1H, broad t), 7.14 (1H, d, J = 8.4 Hz), 7.50 (1H, d, J = 0.7Hz), 7.69 (4H, m). 3-10

379.4596 B 380 (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 3.24 (3H, s), 3.51(2H, q, J = 7.3 Hz), 4.00 (3H, s), 7.41 (1H, d, J =8.4 Hz), 7.52 (1H, d,J = 0.6 Hz), 7.51-7.71 (4H, m). 3-11

359.4067 A 360 (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 3.51 (2H, q, J = 7.3Hz), 3.93 (3H, s), 3.96 (3H, s), 7.24(1 H, d, J =8.4 Hz), 7.51 (1H, d, J= 0.7 Hz), 7.63 (1H, d, J = 1.9 Hz), 7.66 (2H, m), 7.75 (1H, d, J = 1.9Hz). 3-12

372.4491 C 373 (CDCl3) d 1.57 (3H, t, J = 7.3 Hz), 3.02 (3H, s), 3.14(3H, s), 3.52 (2H, q, J = 7.3 Hz), 3.96 (3H, s), 6.96 (1H, d, J = 8.4Hz), 7.47 (1H, t, J =0.6 Hz), 7.60-7.70 (4H, m).

Example 4

[0225] As a starting material, 3-hydroxy-4-methoxy benzonitrile wasprepared.

[0226] First, a mixture of 3-hydroxy-4-methoxy benzaldehyde (25 g, 164.3mmol), hydroxylamine hydrochloride (13.7 g, 197.2 mmol), and acetic acidsodium salt (27 g, 328.6 mmol) in acetic acid (200 ml) was refluxedovernight. After cooling, the acetic acid was evaporated under reducedpressure. Water was added to the residue and the resulting precipitatewas collected by filtration. The crude product was recrystalized to give3-hydroxy-4-methoxy benzonitrile. (23.54 g, 96%)

[0227] Then with the use of this nitrile compound and according to theprocedure that is similar to that of Example 3, following compoundsshown in Table 4 below were prepared. TABLE 4 Activity Ex. No.MOLSTRUCTURE MOLWEIGH grade MS NMR 4-1

391.4956 B 392 (CDCl3) d 1.52 (3H, t, J = 7.3 Hz), 3.40 (2H, q, J = 7.3Hz), 3.96 (3H, s), 5.27 (2H, s), 7.00 (1H, d, J ==8.2 Hz), 7.31 (1H, d,J = 7.6 Hz), 7.38 (2H, t, J = 7.4 Hz), 7.47 (3H, m), 7.56 (1H, s), 7.63(1H, dd, J =2.2, 12.6 Hz), 7.67 (1H, d, J = 2.0 Hz). 4-2

301.3697 A 302 (CDCl3) d 1.57 (3H, t, J = 7.3 Hz), 3.52 (2H, q, J = 7.3Hz), 3.96 (3H, s), 5.81 (1H, s), 6.96 (1H, d, J =8.5 Hz), 7.47 (1H, t, J= 0.6 Hz), 7.58-7.64 (3H, m), 7.69 (1H, d, J =2.1 Hz). 4-3

343.451 A 344 (CDCl3) d 1.43 (6H, d, J = 6.0 Hz), 1.59 (3H, t, J = 7.3Hz), 3.51 (2H, q, J = 7.3 Hz), 3.92 (3H, s), 4.63 (1H, quint, J = 6.0Hz), 6.98 (1H, d, J = 8.4 Hz), 7.47 (1H, s), 7.63-7.71 (4H, m). 4-4

383.5163 B 384 (CDCl3) d 1.34 (4H, m), 1.57 (5H, m), 1.87 (2H, m), 2.11(2H, m), 3.51 (2H, q, J = 7.3 Hz), 3.92 (3H, s), 4.30 (1H, m), 6.98 (1H,d, J =8.4 Hz), 7.47 (1H, s), 7.63 (3H, m), 7.72 (1H, d, J = 2.1 Hz). 4-5

399.5157 B 400 (CDCl3) d 1.40-1.71 (5H, m), 1.78 (1H, m), 1.93 (1 H, m),3.52 (3H, m), 3.83 (1H, m), 3.92 (3H, s), 3.99-4.18 (3H, m), 6.96 (1H,d, J =8.4 Hz), 7.47 (1H, t, J = 0.6 Hz), 7.63 (2H, m), 7.66 (1H, dd, J =2.1, 8.4 Hz), 7.72 (1H, d, J = 2.1 Hz). 4-6

373.4774 A 374 (CDCl3) d 1.25 (3H, t, J =7.0 Hz), 1.58 (3H, t, J =7.3Hz), 3.51 (2H, q, J =7.3 Hz), 3.63 (2H, q, J = 7.0 Hz), 3.87 (2H, t, J =5.2 Hz), 3.93 (3H, s), 4.29 (2H, t, J =5.2 Hz), 6.98 (d, 1H, J = 8.4Hz), 7.47 (1H, s), 7.63 (2H, s), 7.67 (1H, dd, J = 2.0, 8.4 Hz), 7.73 (1H, d, J = 2.0 Hz). 4-7

343.4073 A 344 (CDCl3) d 1.56 (3H, t, J = 7.3 Hz), 2.37 (3H, s), 3.51(2H, q, J = 7.3 Hz), 3.90 (3H, s), 7.04 (1H, d, J =8.6 Hz), 7.48 (1H, t,J = 0.6 Hz), 7.62 (2H, m), 7.77 (1H, d, J = 2.2 Hz), 7.93 (1H, dd, J =2.2, 8.6 Hz). 4-8

372.4491 A 373 (CDCl3) d 1.25 (3H, t, J = 7.1 Hz), 1.56 (3H, t, J = 7.3Hz), 3.35 (2H, quint, J = 6.6 Hz), 3.51 (2H, q, J = 7.3 Hz), 3.92 (3H,s), 5.07 (1H, broad t), 7.05 (1H, d, J = 8.6 Hz), 7.47 (1H, s), 7.63(2H, m), 7.82 (1H, d, J = 2.2 Hz), 7.92 (1H, dd, J = 2.2, 8,6 Hz). 4-9

379.4596 B 380 (CDCl3) d 1.57 (3H, t, J = 7.3 Hz), 3.22 (3H, s), 3.52(2H, q, J = 7.3 Hz), 3.97 (3H, s), 7.09 (1H, d, J =8.6 Hz), 7.51 (1H,s), 7.80 (1H, s), 7.98 (1H, d, J =8.2 Hz), 8.14 (1H, s), 8.29 (1H, s).4-10

372.4491 B 373 (CDCl3) d 1.57 (3H, t, J = 7.3 Hz), 3.04 (3H, s), 3.17(3H, s), 3.52 (2H, q, J = 7.3 Hz), 3.91 (3H, s), 7.05 (1H, d, J = 8.6Hz), 7.47 (1H, s), 7.64 (2H, broad d), 7.79 (1H, d, J =2.2 Hz), 7.93(1h, dd, J = 2.2, 8.6 Hz).

Example 5

[0228]

[0229] A mixture of4-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7-yl)-2-methoxyphenol (750mg, 2.49 mmol) obtained in the process of Example 3,1-bromo-2-chloroethane (0.62 ml, 7.47 mmol) and CS₂CO₃ (2.43 g, 7.47mmol) in acetone (25 ml) was refluxed for 3 h. After cooling to roomtemperature, the mixture was poured into water and extracted with EtOAc.The organic extract was dried over MgSO₄, concentrated in vacuo and theresidue was purified by column chromatography to give7-[4-(2-Chloro-ethoxy)-3-methoxy-phenyl]-5-ethylsulfanyl-imidazo[1,2-c]pyrimidine(805 mg, 88%).

[0230] Then a solution of7-[4-(2-Chloro-ethoxy)-3-methoxy-phenyl]-5-ethylsulfanyl-imidazo[1,2-c]pyrimidine(800 mg, 2.2 mmol) in morpholine (10 ml) was stirred at 100° C.overnight. After cooling to room temperature, the mixture was pouredinto a dilute NaOH solution and extracted with CH₂Cl₂. The combinedorganic extract was dried over MgSO₄ and concentrated in vacuo. Thecrude product was purified by column chromatography to give5-Ethylsulfanyl-7-[3-methoxy-4-(2-morpholin-4-yl-ethoxy)-phenyl]-imidazo[1,2-c]pyrimidine(650 mg, 71%).

[0231] Molecular weight: 414.5274

[0232] Mass spectrometry: 415

[0233] Activity grade: A

[0234]¹H-NMR: (CDCl3) d 1.59 (3H, t, J=7.3 Hz), 2.61 (4H, t, J=4.6 Hz),2.88 (2H, t, J=6.0 Hz), 3.51 (2H, q, J=7.3 Hz), 3.75 (4H, t, J=4.6 Hz),3.96 (3H, s), 4.23 (2H, t, J=6.0 Hz), 6.99 (1H, d, J=8.4 Hz), 7.48 (1H,s), 7.61-7.68 (4H, m).

[0235] According to the procedure that is similar to that describedabove, following compounds shown in Table 5 below were prepared. TABLE 5Ex. MOL- Activity No. MOLSTRUCTURE WEIGH grade MS NMR 5-1

428.5542 A 429 (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 2.05 (2H, quint, J =6.8 Hz), 2.48 (4H, t, J = 4.5 Hz), 2.56 (2H, t, J = 7.1 Hz), 3.51 (2H,q, J = 7.3 Hz), 3.72 (4H, t, J = 4.6 Hz), 3.96 (3H, s), 4.17 (2H, t, J =6.6 Hz), 7.00 (1H, d, J = 8.4 Hz), 7.48 (1H, s), 7.61 5-2

414.571 A (CDCl3) d 1.04 (6H, t, J = 7.1 Hz), 1.59 (3H, t, J = 7.3 Hz),2.01 (2H, quint, J = 6.9 Hz), 2.49-2.67 (6H, m), 3.51 (2H, q, J = 7.3Hz), 3.96 (3H, s), 4.15 (2H, t, J = 6.6 Hz), 7.01 (1H, d, J = 8.3 Hz),7.47 (1H, s), 7.60-7.68 (4H, m). 5-3

416.5432 A (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 2.07 (2H, quint, J = 6.6Hz), 2.32 (3H, s), 2.60 (2H, t, J = 5.3 Hz), 2.68 (2H, t, J =7.1 Hz),3.51 (2H, q, J = 7.3 Hz), 3.63 (2H, t, J = 5.3 Hz), 3.96 (3H, s), 4.15(2H, t, J =6.4 Hz), 6.98 (1 H, d, J = 8.3 Hz), 7.47 (1H, s), 7.61-7.68(4H, m). 5-4

441.5969 B (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 2.08 (2H, quint, J = 6.8Hz), 2.35 (3H, s), 2.40-2.60 (10, m), 3.51 (2H, q, J = 7.3 Hz), 3.93(3H, s), 4.18 (2H, t, J = 6.8 Hz), 6.97 (1H, d, J = 8.6 Hz), 7.47 (1H,s), 7.62-7.68 (4H, m). 5-5

455.6237 B (CDCl3) d 1.56 (3H, t, J = 7.3 Hz), 1.73 (1H, m), 3.51 (2H,q, J = 7.3 Hz), 3.91 (3H, s), 4.19 (2H, t, J =9.0 Hz), 6.97 (1H, d, J =8.6 Hz), 7.47 (1H, s), 7.62-7.68 (4H, m). 5-6

426.582 B (CDCl3) d 1.43-1.62 (9H, m), 2.08 (2H, quint, J = 6.8 Hz),2.42 (4H, broad s), 2.53 (2H, broad t), 3.51 (2H, q, J = 7.3 Hz), 3.94(3H, s), 4.18 (2H, t, J = 6.8 Hz), 6.97 (1H, d, J = 8.3 Hz), 7.47 (1H,s), 7.60-7.69 (4H, m). 5-7

426.582 A (CDCl3) d 1.46-1.62 (9H, m), 2.10 (2H, broad quint), 2.46-2.56(6H, broad m), 3.51 (2H, q, J 7.3 Hz), 3.95 (3H, s), 4.16 (2H, t, J =6.8 Hz), 7.01 (1H, d, J = 8.3 Hz), 7.47 (1H, d, J = 0.7 Hz), 7.60-7.67(4H, m). 5-8

441.5969 A (CDCl3) d 1.58 (3H, t, J = 7.3 Hz), 2.05 (2H, quint, J = 6.8Hz), 2.31 (3H, s), 2.48-2.63 (10H, m), 3.51 (2H, q, J = 7.3 Hz), 3.94(3H, s), 4.16 (2H, t, J = 6.8 Hz), 7.00 (1H, d, J = 8.3 Hz), 7.47 (1H,s), 7.60-7.68 (4H, m). 5-9

444.6212 A (CDCl3) d 1.58 (3H, t, J = 7.3 Hz), 2.03 (2H, quint, J = 6.8Hz), 2.58 (2H, t, J = 7.1 Hz), 2.66-2.77 (8H, m), 3.51 (2H, q, J = 7.3Hz), 3.95 (3H, s), 4.14 (2H, t, J = 6.8 Hz), 7.00 (1H, d, J = 8.3 Hz),7.48 (1H, a), 7.60-7.67 (4H, m). 5-10

444.6212 B (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 2.06 (2H, quint, J = 6.8Hz), 2.60 (2H, t, J = 7.1 Hz), 2.65-2.77 (8H, m), 3.51 (2H, q, J = 7.3Hz), 3.93 (3H, s), 4.17 (2H, t, J = 6.8 Hz), 6.98 (1H, d, J = 8.9 Hz),7.48 (1H, s), 7.60-7.65 (4H, m). 5-11

428.5542 B (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 2.08 (2H, quint, J = 6.8Hz), 2.49 (4H, broad s), 2.58 (2H, t, J = 7.1 Hz), 3.51 (2H, q, J = 7.3Hz), 3.72 (4H, t, J =4.4 Hz), 3.92 (3H, s), 4.20 (2H, t, J = 6.8 Hz),6.98 (1H, d, J = 8.9 Hz), 7.47 (1H, s), 7.63-7.67 (4H, m). 5-12

414.5274 B (CDCl3) d 1.58 (3H, t, J = 7.3 Hz), 2.63 (4H, broad s), 2.90(2H, t, J =6.0 Hz), 3.51 (2H, q, J = 7.3 Hz), 3.75 (4H, t, J = 4.7 Hz),3.93 (3H, s), 4.27 (2H, t, J = 6.0 Hz), 6.98 (1H, d, J = 8.2 Hz), 7.47(1H, d, J = 0.6 Hz), 7.62-7.70 (4H, m). 5-13

469.6069 A (CDCl3) d 1.59 (3H, t, J = 7.3 Hz), 1.61-2.22 (9H, m), 2.54(2H, t, J = 7.1 Hz), 3.00 (2H, broad d), 3.51 (2H, q, J = 7.3 Hz), 3.94(3H, s), 4.16 (2H, q, J = 6.8 Hz), 5.24(1H, broad s), 5.43 (1H, broads), 6.99 (1H, d, J = 8.3 Hz), 7.47 (1H, d, J = 0.7 Hz), 7.60-7.65 (4H,m). 5-14

442.581 A (CDCl3), 1.16 (3H, s), 1.18 (3H, s), 1.59 (2H, t, J = 7.5 Hz),1.92 (2H, t, J = 10.6 Hz), 2.86 (2H, s), 2.88 (2H, s), 3.48(3H, d, J =3.8 Hz), 3.72(2H, J = 6.0 Hz), 7.00 (1H, d, J = 8.3 Hz), 7.48 (1H, s),7.64 (4H, m)

Example 6

[0236]

[0237] To7-(3,4-Dimethoxy-phenyl)-5-ethylsulfanyl-imidazo[1,2-c]pyrimidine (1.1g, 3.5 mmol) in CH₂Cl₂ (25 ml) at 0° C., was added dropwise 1M solutionof BBr₃ in CH₂Cl₂ (25 ml, 25.0 mmol). The reaction mixture was stirredat 0° C. for 15 min and then at room temperature overnight. The mixturewas then cooled using ice bath and ice-water was added, the precipitatewas collected by filtration and then suspended in CH₂Cl₂ to give4-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7-yl)-benzene-1,2-diol. (875mg, 87%)

[0238] To4-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7-yl)-benzene-1,2-diol (86.2mg, 0.3 mmol) in DMF (2 ml) were added ethyl bromide (112 μl, 1.5 mmol)and K₂CO₃ (290 mg, 2.1 mmol). The reaction mixture was stirred at about50° C. overnight. After cooling to room temperature, it was poured intowater and extracted with EtOAc. The combined organic extract was driedover MgSO₄ and concentrated in vacuo. The residue was purified bypreparative thin layer chromatography to give7-(3,4-Diethoxy-phenyl)-5-ethylsulfanyl-imidazo[1,2-c]pyrimidine (39.1mg, yield 36%).

[0239] According to the procedure that is similar to that descri edabove, following compounds shown in Table 6 below were prepared. TABLE 6Activity Ex. No. MOLSTRUCTURE MOLWEIGHT grade MS NMR 6-1

343.4489 A 344 (CDCl3) d 1.46-1.61 (9H, m), 3.51 (2H, q, J = 7.3 Hz),4.16 (2H, q, J =7.0 Hz), 4.21 (2H, q, J = 7.0 Hz), 6.98 (1H, d, J = 8.5Hz), 7.47 (1H, d, J = 0.6 Hz), 7.61-7.68 (4H, m). 6-2

431.5541 B 432 (CDCl3) d 1.24 (3H, 1, J = 7.0 Hz), 1.25 (3H, t, J = 7.0Hz), 1.58 (2H, q, J = 7.3 Hz), 3.51 (2H, q, J = 7.3 Hz), 3.63 (4H, m),3.84 (4H, m), 4.24 (4H, m), 7.02 (1H, d, J = 8.5 Hz), 7.47 (1H, d, J =0.6 Hz), 7.60-7.67 (3H, m), 7.72 (1H, d, J = 2.2 Hz). material forExample 6

287.3417 C (DMSO d-6) d 1.52 (3H, t, J = 7.3 Hz), 3.58 (2H, q, J = 7.3Hz), 6.92 (1H, d, J = 8.3 Hz), 7.62 (1H, dd, J =2.2, 8.3 Hz), 7.70 (1H,d, J = 2.2 Hz), 7.87 (1H, s), 8.15 (2H, dd, J =2.2, 10.7 Hz).

Example 7

[0240]

[0241] To a solution of 4-Hydroxy-3-methoxy-benzonitrile (89 g, 0.60mol) in 1000 ml of CH₂Cl₂ was added 130 ml of triethylamine and triflicchloride (125 g, 0.79 mol) in the presence of a catalytic amount ofDimethylaminopyridine at 0° C. After being stirred for 1 h at 0° C., thereaction was quenched with water. The reaction mixture was washed with asaturated NaHCO₃ solution(30 ml) and brine (300 ml). The organic layerwas dried over MgSO₄ and concentrated. The crude mixture was used fornext step without further purification.

[0242] The crude triflate in 500 ml of morpholine was heated at 120° C.for 2 h. After cooling to room temperature, morpholine was removed underreduced pressure. The residue was diluted with 3N HCl (200 ml) and EtOAc(300 ml). After separation of the aqueous layer, the organic layer wasextracted with 3N HCl. The combined aquous layer was basified byaddition of 6N NaOH solution and then extracted with EtOAc. The combinedorganic layer was washed with brine (300 ml), dried over MgSO₄ andconcentrated. The crude product was filtrated on silica. The filtratewas concentrated and the residue was recrytallized from ether to give3-Methoxy-4-morpholin-4-yl-benzonitrile (39 g, 30%) as a white solid.

[0243] With the use of 3-Methoxy-4-morpholin-4-yl-benzonitrile, andaccording to the procedure that is similar to that of Example 1 above,5-Ethylsulfanyl-7-(3-methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidinewas prepared.

[0244] Molecular weight: 370.4768

[0245] Mass spectrometry: 371

[0246] Activity grade: A

[0247]¹H-NMR: CDCl3 7.67-7.63 (m, 4H), 7.60 (s, 1H), 7.48 (s, 1H), 7.01(d, 1H, J=15.1 Hz), 3.97 (s, 3H), 3.92 (t, 4H, J=7.6 Hz), 3.51 (q, 2H,J=12.2 Hz), 3.15 (t, 2H, J=7.6 Hz), 1.59 (t, 3H, J=12.3 Hz)

Example 8

[0248]

[0249] Sodium (3.92 g, 0.1 mol) was dissolved in 150 ml of ethanol.Ethyl cyanoacetate (17.5 g, 0.15 mol) and thiourea (12.8 g, 0.17 mol)were added and the mixture was refluxed for 2 h. After cooling to roomtemperature, 30 ml of water was added. Diethyl sulfate (23.9 g, 0.16mol) was added at room temperature and the reaction mixture was refluxedfor 15 min. After cooling to room temperature, the reaction mixture wasconcentrated in vacuo. The residue was recrystallized from water/MeOH togive the product (13 g, 50%) as a white solid.

[0250] To a solution of 6-Amino-2-ethylsulfanyl-pyrimidin-4-ol (1.1 g,6.42 mmol) in 3 ml of THF was added NaH (0.23 g, 9.64 mmol) at 0° C.After 15 min. at 0° C., N-phenyltrifluromethane sulfonamide (3.4 g, 9.64mmol) was added. The reaction mixture was stirred at 0° C. for 1 h andwarmed to room temperature. After 3 h, the reaction mixture was quenchedwith 0.5 ml of water and concentrated in vacuo. The residue was purifiedby column chromatography to give the product (1.7 g, 7%) as a whitesolid.

[0251] A mixture of triflate (100 mg, 0.33 mmol), aryl boronic acid (63mg, 0.46 mmol), tri-o-tolylphosphine (24 mg, 0.08 mmol), Pd₂(dba)₃ (34mg, 0.03 mmol) and cesium carbonate (183 mg, 0.56 mmol) in dioxane (5ml) was degassed with vigorous stirring and filled with Ar atmosphere.The mixture was heated to 80° C. for 1 day. Cooled to room temperature,the mixture was diluted with 30 ml of CHCl₃ and filtered through aCelite pad. The filtrate was concentrated and the residue was purifiedby preparative thin layer chromatography to give the coupled product (40mg, 49%).

[0252] A mixture of aminopyrimidine (20 mg, 0.08 mmol) and dimethylbromoacetal (27 mg, 0.16 mmol) in 1,4-dioxane/water (4 ml/1 ml) wasrefluxed for 1 day. The reaction mixture was concentrated, and theresidue was diluted with 5 ml of MeOH. The mixture was treated withK₂CO₃ (2 mg) and diisopropylethylamine (0.5 ml). The mixture wasfiltered and the filtrate was concentrated. The residue was purified bypreparative thin layer chromatography to give3-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7-yl)-phenylamine (7 mg,32%).

[0253] Molecular weight: 270.3586

[0254] Mass spectrometry: 271

[0255] Activity grade: A

[0256]¹H-NMR: CDCl3 7.60 (s, 1H), 7.58 (d, 1H, J=1.4 Hz), 7.42 (s, 1H),7.39 (d, 1H, J=8.0 Hz), 7.33 (t, 1H, J=1.9 Hz), 7.19 (t, 1H, J=7.8 Hz),6.97 (dd, 1H, J=7.8, 1.8 Hz), 3.72 (br s, 2H), 3.44 (q, 2H, J=7.3 Hz),1.49 (t, 3H, J=7.3 Hz

[0257] According to the procedure that is similar to that describedabove, following compounds shown in Table 8 below were prepared. TABLE 8Ex. No. MOLSTRUCTURE MOLWEIGH Activity grade MS NMR 8-1

285.3703 B 286 CDCl3 7.72-7.66 (m, 4H), 7.50 (s, 1H), 7.40 (t, 1H, J =7.9 Hz), 6.97 (dd, 1H, J = 8.3, 2.4 Hz), 3.90 (s, 3H), 3.52 (q, 2H, J =7.3 Hz), 1.58 (t, 3H, J = 7.3 Hz) 8-2

256.3314 C 257 CDCl3 9.35 (s, 1H), 8.65 (dd, 1H, J = 4.8, 1.4 Hz), 8.33(dd, 1H, J =7.9, 1.8 Hz), 7.77 (s, 1H), 7.70 (s, 1H), 7.54 (s, 1H), 7.43(dd, 1H, J =Hz), 1.58 (t, 3H, J = 7.3 Hz) 8.0, 4.9 Hz), 3.53 (q, 2H, J =7.4 8-3

261.3696 B 262 CDCl3 7.63 (d, 1H, J = 1.3 Hz), 7.61 (d, 1H, J = 1.1 Hz),7.57 (s, 1H), 7.60 (d, 1H, J = 0.6 Hz), 7.39 (dd, 1H, J = 5.0, 1.0 Hz),7.12 (dd, 1H, J = 5.0, 3.7 Hz), 3.48 (q, 2H, J = 7.3 Hz), 1.57 (t, 3H, J= 7.3 Hz) 8-5

261.3719 B 262 CDCl3 7.98 (d, 1H, J = 1.0 Hz), 7.63 (s, 1H), 7.61 (d,1H, J = 1.0 Hz), 7.54 (s, 1H), 7.48 (s, 1H), 7.41 (dd, 1H, J = 4.9, 1.9Hz), 3.50 (q, 2H, J =7.3 Hz), 1.57 (t, 3H, J = 7.3 Hz) 8-6

299.3538 B CDCl3 8.99 (t, 1H, J = 2.0 Hz), 8.35 (dd, 1H, J = 7.9, 1.0Hz), 7.82 (s, 1H), 7.72 (d, 1H, J = 1.3 Hz), 7.66 (t, 1H, J = 2.0 Hz),7.56 (s, 1H), 3.56 (q, 2H, J = 7.4 Hz), 1.61 (t, 3H, J = 7.3 Hz) 8-7

291.3247 C-D 292 CDCl3 7.93 (td, 1H, J = 10.8, 2.2 Hz), 8.35 (dt, 1H, J= 8.8, 2.0 Hz), 7.68 (s, 1H), 7.66 (s, 1H), 7.51 (s, 1H), 7.25 (q, 1H, J= 8.8 Hz), 3.52 (q, 2H, J = 7.3 Hz), 1.58 (t, 3H, J =7.4 Hz) 8-8

330.3666 C CDCl3 7.95 (d, 1H, J = 8.2 Hz), 7.59-7.30 (m, 3H), 7.02 (s,1H), 6.96 (d, 1H, J = 5.6 Hz), 3.97 (s, 3H), 3.33 (q, 2H, J = 7.2 Hz),1.58 (t, 3 H, J = 7.3 Hz)

[0258] (Preparation of Intermidiates I)

[0259] To a solution of7-(3,4-dimethoxyphenyl)-5-ethylthioimidazo[1,2-c])pyrimidine (25.5 g, 64mmol) (prepared in Example 1) in MeOH (500 ml) was added aquous KOHsolution (2N, 135 ml, 270 mmol) and the resulting solution was heatedunder reflux overnight. The resulting mixture was cooled to roomtemperature and was partially concentrated under reduced pressure. Theprecipitate that emerged was collected, washed with water and then MeOH.This potassium salt was suspended in water and the suspension wasneutralized with 1N HCl to obtain the free (non-salt) form of theproduct. The precipitate was collected and washed with water and thenMeOH, and then dried in vacuo. (13 g, 75%)

[0260] A solution of5-hydroxy-7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidine (44 g, 162mmol) and POCl₃ (500 g) was heated under ref lux for 4 hr. The reactionmixture was concentrated in vacuo, followed by the addition ofice-water. The solid was collected by filtration. The solid was thensuspended in water and washed with saturated NaHCO₃ solution. Thecollected solid was dried in vacuo (47 g, 92%).

[0261] With the use of various compounds obtained by the same method asany of Examples 1-8 or by the similar method to any of Examples 1-8above, various imidazopyrimidine intermediates having various C-7substituents can be prepared.

[0262] (Preparation of Intermidiates II)

[0263] To the solution of 4-bromoveratrole (27.8, 128 mmol) in 160 ml ofdry THF was added 75 ml of n-butyl lithium solution in hexane (1.59M)within 30 min. at −70° C. under Ar with stirring. The resulting whiteslurry was stirred at −70° C. for 1 hr. The solution of2,4-dichloropyrimidine (14.9 g, 100 mmol) in 50 ml dry THF was added tothe slurry at −30° C. under Ar with stirring within 30 min. Theresulting solution was stirred at −30° C. for 1 h then 0° C. for 45 min.The reaction was quenched with a solution of acetic acid (6.4 ml, 104mmol) and water(1 ml, 56 mmol) in THF. The mixture was stirred at roomtemperature for 5 min, cooled to 0° C., and treated with the solution ofDDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone, 22.7 g, 100 mmol) in 30 mlof THF. The mixture was stirred at room temperature for 10 min, cooledto 0° C., treated with 40 ml of 3M sodium hydroxide aqueous solution andstirred at 0° C. for 10 min, 300 ml of ethyl acetate was added to themixture, the organic layer was separated, and dried with MgSO₄. Afterthe solvent was evaporated, the residue was purified by columnchromatography (Ethyl acetate/Hexane 1:4) to give the product (13.8 g,48.4%).

[0264] To 45 ml anhydrous hydrazine was added2,4-dichloro-6-(3,4-dimethoxy-phenyl)-pyrimidine (7 g, 24.55 mmol) at 0°C. and the resulting slight yellow suspension was stirred for 30 min.The slight yellow precipitate was collected by filtration. The crudeproduct was purified by column chromatography (EtOAc/Hex/Methanol2:1:0.1) to give the product (3.9 g, 56.6%).

[0265] [2-Chloro-6-(3,4-dimethoxy-phenyl)-pyrimidin-4-yl]-hydrazine(1123 mg, 4 mmol) was added to 10 ml of formic acid and the mixture wasstirred at 85° C. overnight, the resulting yellow solution was pouredinto 50 ml of ice water with stirring. The precipitate was collected byfiltration and washed with water and ethanol to give product (1010 mg,92.7%).

[0266] The suspension of7-(3,4-dimethoxyphenyl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-ol (1010 mg,3.71 mmol) in 10 ml phosphorus oxychloride and N,N-diethylaniline (0.5ml) was heated at 120° C. for 3 h. The phosphorus oxychloride wasevaporated at vacuum and the residue was added to the mixture of 20 mlof crush ice and 15 ml of saturated NaHCO₃ aqueous solution. The mixturewas extracted with 2×150 ml ethyl acetate and the combined extract wasdried with MgSO₄. The solvent was evaporated at vacuum to give productas slight yellow solid (850 mg, 78.8%).

[0267] With the use of various compounds obtained by the same method asany of Examples 1-8 or by the similar method to any of Examples 1-8above, various triazolopyrimidine intermediates having various C-7substituents can be prepared.

Example 9

[0268] The mixture of 5-chloro-7-(3,4-dimethoxyphenyl)imidazo[1,2-c]pyrimidine (57.94 mg, 0.2 mmol),1-(4-fluorophenyl)piperazine.2HCl (55.69 mg, 0.22 mmol), anddiisopropylethylamine (85.31 mg, 0.66 mmol) in 3 ml of 2-propanol wasstirred at 90° C. for 3 h, and cooled to room temperature. To theobtained mixture, 3 ml of ice water was added, the produced white solidwas collected by filtration, and dried to give the pure product (56 mg,64.6%) of7-(3,4-Dimethoxyphenyl)-5-[4-(4-fluorophenyl)piperazin-1-yl]-imidazo[-1,2-c]pyrimidine.

[0269] Molecular weight: 433.4846

[0270] Mass spectrometry: 434

[0271] Activity grade C.

Example 10

[0272] The mixture of5-chloro-7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidine (57.94 mg, 0.2mmol), 4-aminomethylpyridine (23.79 mg, 0.22 mmol), anddiisopropylethylamine (38.78, 0.3 mmol) in 2-propanol was stirred at 90°C. for 20 h, and cooled to room temperature. The solvent was evaporated,and 5 ml of ice water was added. Then the resulting product wasextracted with 2×10 ml of ethyl acetate. The combined extract was driedover MgSO₄. Then the solvent was evaporated and 2 ml of ether was added.The produced solid was collected by filtration and dried to give pureproduct (38 mg, 52.6%) of[7-(3,4-dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]pyridin-4-ylmethyl-amine.

[0273] Molecular weight 361.4031

[0274] Mass spectrometry: 362

[0275] Activity grade: A

[0276] With the use of any of the intermediates I or II and according tothe procedure that is similar to that of Example 9 or 10, followingcompounds shown in Table 9 below were prepared. TABLE 9 Activity Ex. No.MOLSTRUCTURE MOLWEIGHT grade MS NMR 9-1

383.454 B 384 9-2

448.4827 C 449 9-3

341.4163 C 342 9-4

344.3733 B 345 9-5

404.4727 B 405 9-6

367.4733 A 9-7

341.4351 A 9-8

327.408 A 9-9

329.4239 A 9-10

360.4192 B 9-11

298.3475 A 9-12

284.3204 B 9-13

372.4303 B 9-14

381.8247 382 (CDCl3) 3.97 (3H, s), 4.06 (3H, s), 6.99 (1H, d, J = 8.5Hz), 7.17 (1H, d, J = 7.9 Hz), 7.32-7.66 (3H, m), 7.80 (1H, d, J = 1.9Hz), 8.18 (1H, br), 8.32 (2H, s), 8.37-8.39 (1H, m) 9-15

377.4062 378 (DMSO d-6) 2.09 (3H, s), 3.76 (3H, s), 3.77 (3H, s),6.77-6.80 (1H, m), 6.99-7.14 (3H, m), 7.60-7.63 (2H, m), 7.72 (1H, s),8.56 (1H, s), 9.42 (1H, s), 9.62 (1H, br) 9-16

363.3819 A 364 (DMSO d-6) 3.85 (3H, s), 3.90 (3H, s), 6.29 (1H, d, J =7.9 Hz), 7.12 (1H, d, J = 8.3 Hz), 7.52-7.67 (2H, m), 7.81-7.84 (2H, m),7.92 (1H, s), 8.58 (1H, s), 8.62 (1H, br) 9-17

364.3666 C 365 (DMSO d-6) 3.78 (3H, s), 3.80 (3H, s), 7.00 (1H, d, J =8.4 Hz), 7.19-7.23 (1H, m), 7.34-7.37 (1H, m), 7.64-7.69 (2H, m), 7.78(1H, s), 7.97 (1H, d, J = 3.6 Hz), 8.55 (1H, s), 9.80 (1H, br), 10.12(1H, br) 9-18

398.4278 C-D 399 (DMSO d-6) 3.84 (3H, s), 3.86 (3H, s), 7.12 (1H, d, J =8.3 Hz), 7.52-7.56 (1H, m), 7.82-7.91 (3H, m), 8.07 (1H, d, J = 9.0 Hz),8.32-8.35 (2H, m), 8.64-8.68 (2H, m), 8.83-8.86 (1H, m), 10.56 (1H, s)9-19

439.4097 A 418 (DMSO d-6) 3.83 (3H, s), 3.89 (3H, s), 6.36 (1H, d, J =15.9 Hz), 7.13 (1H, d, J = 15.6 Hz), 7.09 (1H, d, J = 8.2 Hz), 7.53 (2H,d, J = 8.6 Hz), 7.77, 7.81, 7.99 (2H, d, J = 8.6 Hz), 8.55 (1H, s) 9-20

441.4256 A 420 (DMSO d-6) 2.17 (2H, t, J = 8.3 Hz), 2.77 (2H, t, J =7.45 Hz), 3.83 (3H, s), 3.87 (3H, s), 7.07 (1H, d, J =8.3 Hz), 7.23 (2H,d, J = 8.4 Hz), 7.74-7.85 (5H, m), 8.54 (1H, s), 10.07 (1H, br) 9-21

435.446 436 9-22

471.5639 A 472 9-23

432.4833 A 433 9-24

432.4833 A 433 9-25

446.5103 B 447 9-26

519.5649 B 520 9-27

411.9135 A 412 (DMSO) 3.83 (3H, s), 3.85 (3H, s), 4.95 (2H, s), 7.09(1H, d, J = 8.5 Hz), 7.28-7.39 (2H, m), 7.54 (1H, dd, J = 1.6 Hz, 7.7Hz), 7.69-7.87 (5H, m), 8.03 (1H, s). 9-28

387.4609 A 388 (DMSO) 1.17 (3H, t, J = 4.1 Hz), 2.99 (2H, t, J = 6.9Hz), 3.72 (2H, t, J = 6.9 Hz), 3.83 (3H, s), 3.87 (3H, s), 4.10 (2H, q,J = 7.1 Hz), 7.07 (1H, d, J = 8.3 Hz), 7.69 (1H, d, J = 1.4 Hz),7.76-7.82 (3H, m), 8.00 (1H, s). 9-29

404.4727 A 405 9-30

340.3851 C 341 9-31

396.4498 B 397 9-32

473.5362 C 474 2.58-2.69 (4H, m), 3.46-3.57 (6H, m), 3.81 (3H, s), 3.86(3H, s), 6.00 (2H, s), 6.79-6.92 (3H, m), 7.04 (1H, d, J = 8.2 Hz), 7.59(1H, s), 7.73-7.76 (4H, m) 9-33

415.4992 C 416 (DMSO d-6) 3.42 (4H, t, J = 4.5 Hz), 3.67 (4H, t, J = 4.5Hz), 3.82 (3H, s), 3.88 (3H, s), 6.83 (1H, t, J = 7.2 Hz), 7.02-7.07(3H, m), 7.24-7.29 (2H, m), 7.63 (1H, s), 7.75-7.81 (3H, m), 7.85 (1H,s) 9-34

445.5256 C 446 9-35

460.4967 C 461 9-36

457.5368 C 458 9-37

353.4275 B 354 (DMSO d-6) 2.33 (3H, s), 2.65 (4H, s), 3.53 (4H, s), 3.81(3H, s), 3.87 (3H, s), 7.05 (1H, d, J = 8.4 Hz), 7.60 (1H, s), 7.73,7.77 (4H, m) 9-38

416.4868 B 417 9-39

449.9442 C 450 9-40

445.5256 C 446 9-41

417.4743 B 418 9-42

484.3893 C-D 484, 486 9-43

445.5256 C 446 (DMSO d-6) 3.43 (4H, t, J = 4.9 Hz), 3.70 (4H, t, J = 4.9Hz), 3.74 (3H, s), 3.83 (3H, s), 3.89 (3H, s), 6.43 (1H, d, J = 8.1 Hz),6.56 (1H, s), 6.62 (1H, d, J = 8.2 Hz), 7.09 (1H, d, J = 8.6 Hz), 7.16(1H, t, J = 8.2 Hz), 7.76-7.84 (4H, m), 7.99 (1H, s) 9-44

429.5262 C 430 9-45

41.606 C-D 542 9-46

433.4709 C 434 9-47

433.4896 C 434 (DMSO d-6) 3.30 (4H, t, J = 4.7 Hz), 3.67 (4H, t, J = 4.7Hz), 3.82 (3H, s), 3.88 (3H, s), 6.99-7.21 (5H, m), 7.63 (1H, s),7.75-7.84 (4H, m) 9-48

421.547 C-D 422 9-49

381.438 B 382 9-50

484.4851 C-D 485 9-51

383.454 C 384 9-52

389.4609 B 390 (DMSO d-6) 1.32 (3H, t, J = 7.1 Hz), 3.61 (2H, q, J = 7.1Hz), 3.79 (6H, s), 4.84 (2H, s), 6.99 (1H, d, J = 8.5 Hz), 7.42 (2H, d,J = 8.5 Hz), 7.56-7.67 (5H, m), 8.49 (2H, d, J = 8.5 Hz) 9-53

418.4998 A 419 2.50 (2H, p, J = 1.8 Hz), 3.30 (3H, s), 3.60 (2H, t, J =7.2 Hz), 3.81 (3H, s), 3.85 (3H, s), 4.68 (1H, t, J = 4 Hz), 5.37 (1H,d, J = 4 Hz), 7.03 (1H, d, J = 9 Hz), 7.27-7.36 (5H, m), 7.53 (1H, s),7.63 (1H, s), 7.70-7.74 (2H, m), 7.80 (1H, s) 9-54

338.4128 B 339 9-55

324.3857 B 325 9-56

326.4017 B 327 (DMSO d-6) 1.27 (6H, t, J = 7.0 Hz), 3.57 (4H, q, J = 7.0Hz), 7.05 (1H, d, J = 7.0 Hz), 7.57 (1H, s), 7.66 (2H, s), 7.73-7.75(2H, m) 9-57

381.438 A 382 9-58

352.3962 B 353 (DMSO d-6) 2.67 (4H, t, J = 6 Hz), 3.81 (3H, s),3.85-3.89 (7H, m), 7.05 (1H, d, J = 8.3 Hz), 7.63 (1H, s), 7.73-7.80(3H, m), 7.87 (1H, s) 9-59

428.5387 C-D 429 9-60

430.511 B 431 9-61

460.5126 C-D 461 9-62

352.4399 C 353 9-63

421.547 C 422 9-64

464.956 C 465 9-65

368.4393 B 369 9-66

396.4498 C 397 9-67

396.4498 C 397 (DMSO d-6) 1.90 (4H, t, J = 5.5 Hz), 3.57 (4H, t, J = 5.5Hz), 3.81 (3H, s), 3.87 (3H, s), 3.96 (4H, s), 7.05 (1H, d, J = 8.3 Hz),7.60 (1H, s), 7.73-7.77 9-68 439.5215 C 440 9-69 354.4122 B 355 9-70

435.4093 C 436 9-71

382.4227 C-D 383 9-72

411.4645 C 412 9-73

425.4916 C-D 426 9-74

367.4546 B  0 9-75

356.4497 B 357 9-76

355.4434 C 356 9-77

370.4116 C 371 9-78

367.4546 C 368 9.79

347.3797 A 347 (CDCl3) d 3.96 (3H, s), 4.00 (3H, s), 6.99 (1H, d, J =8.4 Hz), 7.20 (1H, t, J = 8 Hz), 7.44 (1H, t, J =8 Hz), 7.51 (1H, s),7.67 (1H, dd, J =2 Hz, 8.4 Hz), 7.75 (1H, d, J =2 Hz), 7.92 (1H, d, J =8 Hz), 8.13 (1H, s), 8.31 (1H, s) 9-80

420.4721 B 420 (DMSO-d6) d 3.73 (3H, s), 3.81 (3H, s), 3.83 (3H, s),3.84 (3H, s), 4.77 (2H, d, J =5.2 Hz), 6.47 (1H, dd, J =2.4 Hz, 8.4 Hz),6.61 (1H, d, J = 2.4 Hz), 7.09 (1H, d, J =8.5 Hz), 7.32 (1H, d, J =8.4Hz), 7.51 (1H, s), 7.67 (1H, d, J = 2 Hz), 7.78 (1H, dd, J = 2 Hz, 8.5Hz), 7.99 (1H, s), 8.42 (1H, s), 9.10 (1H, s) 9-81

313.3591 B 314 9-82

381.4773 C 382 9-83

413.4787 A 414 9-84

375.4299 B 376 9-85

471.5145 C 472 9-86

367.4505 B 368 9-87

312.3746 A 313 (CD3OD) 1.06 (3H, t, J = 7.2), 1.84 (2H, q, J = 7.2),3.67 (2H, t, J =7.2), 3.89 (3H, s), 3.92 (3H, s), 7.03 (1H, d, J = 8.4),7.22 (1H, s), 7.46 (1H, s), 7.69 (1H, dd, J = 2.1 and 6.3), 7.75 (2H, d,J = 2.1) 9-88

359.4067 A 360 (DMSO) 3.67 (3H, s), 3.83 (3H, s), 3.90 (3H, s), 7.07(1H, d, J = 9.0 Hz), 7.72 (3H, m), 7.91 (1H, s), 8.01 (1H, s). 9-89

373.4338 B 374 (DMSO) 1.12 (3H, t, J = 7.1 Hz), 3.82 (3H, s), 3.90 (3H,s), 4.12 (2H, q, J = 7.1 Hz), 4.42 (2H, s), 7.05 (1H, d, J = 9.1 Hz),7.72 (1H, d, J = 1.5 Hz), 7.75-7.78 (2H, m), 7.91 (1H, s), 8.01 (1H, s).9-90

373.4338 A 374 (DMSQ) 3.01 (2H, t, J = 6.9 Hz), 3.64 (3H, s), 3.73 (2H,t, J = 6.9 Hz), 3.83 (3H, s), 3.87 (3H, s), 7.07 (1H, d, J = 8.3 Hz),7.70 (1H, d, J = 1.4 Hz), 7.77 (1H, s), 7.80-7.82 (2H, m), 8.00 (1H, s).9-91

373.4338 B 374 (DMSO) 1.31 (3H, d, J = 7.1 Hz), 2.97-3.04 (1H, m), 3.65(1H, dd, J = 6.3 Hz, 13.6 Hz), 3.76 (1H, dd, J = 7.3 Hz, 13.6 Hz), 3.83(3H, s), 3.88 (3H, s), 7.07 (1H, d, J = 8.4 Hz), 7.69 (1H, d, J = 1.4Hz), 7.77-7.82 (2H, m), 7.84 (1H, s), 7.99 (1H, s). 9-92

401.488 B 402 (DMSO) 0.67 (3H, t, d = 7.3 Hz), 1.12 (2H, h, J = 7.6 Hz),1.45 (2H, p, J = 6.8 Hz), 3.82 (3H, s), 3.90 (3H, s), 4.06 (2H, t, J =6.8 Hz), 4.42 (2H, s), 7.03 (1H, d, J = 9.0 Hz), 7.73-7.77 (3H, m), 7.92(1H, s), 8.01 (1H, s). 9-93

407.4514 B (DMSO) 3.57 (3H, s), 3.77 (3H, s), 5.77 (1H, s), 6.92 (1H, d,J = 8.5 Hz), 7.25 (1H, s), 7.37 (1H, t, J = 7.9 Hz), 7.67 (1H, s), 7.68(1H, s), 7.74 (1H, d, J = 7.9 Hz), 8.03 (2H, d, J = 8.2 Hz), 8.16 (1H,d, J = 8.2 Hz), 8.32 (1H, s). 9-94

465.5277 A (CDCl3) 2.76 (2H, t, J = 7.6 Hz), 3.05 (2H, t, J = 7.6 Hz),3.76 (3H, s), 3.78 (3H, s), 3.89 (3H, s), 6.71 (1H, s), 6.72 (1H, s),6.83-6.85 (2H, m), 6.93 (1H, s), 6.96 (1H, d, 7.3 Hz), 7.61-7.67 (3H,m). 9-95

518.571 A (CDCl3) d 2.62 (2H, broad t), 2.88 (2H, t, J = 6.5 Hz), 3.76(4H, t, J = 4.7 Hz), 3.87 (3H, s), 3.98 (3H, s), 4.23 (2H, t, J =5.8Hz), 5.76 (1 H, broad s), 6.34 (1H, broad s), 6.99 (1H, d, J = 8.5 Hz),7.14 (1H, s), 7.18 (1H, dd, J = 2.8, 9.2 Hz), 7.47 (1H, s), 7.60-7.67(4H, m), 9.09 (1H, d, J = 9.2 Hz), 11.69 (1H, s). 9-96

475.5461 A (CDCl3) d 2.60 (2H, broad t), 2.86 (2H, t, J = 6.0 Hz), 3.74(4H, t, J =4.7 Hz), 3.84 (3H, s), 3.92 (3H, s), 4.21 (2H, t, J = 6.0Hz), 6.74 (1H, s), 6.96 (3H, m), 7.42 (1H, s), 7.47 (1H, s), 7.54-7.67(5H, m). 9-97

524.5992 C-D (DMSO d-6) d 2.58 (4H, broad t), 2.79 (2H, broad t), 3.61(4H, t, J =4.7 Hz), 3.85 (3H, s), 4.15 (2H, t, J =5.4 Hz), 5.71 (2H,broad s), 6.55 (2H, m), 7.03 (2H, m), 7.21 (1H, s), 7.53-7.83 (5H, m).9-98

474.5184 A 475 CDCl3 9.06 (d, 1H, J = 9.2 Hz), 7.68-7.65 (m, 3H), 7.46(s, 1H), 7.25 (d, 2H, J = 2.9 Hz), 7.18 (dd, 1H, J = 9.1, 2.8 Hz), 7.02(d, 1H, J =7.9 Hz), 4.00 (s, 3H), 3.93 (t, 4H, J = 4.6 Hz), 3.88 (s,3H), 3.16 (t, 4H, J = 4.4 Hz) 9-99

444.4973 A 445 DMSO 12.93 (s, 1H), 9.06 (d, 1H, J = 8.5 Hz), 8052 (s,1H), 7.99 (d, 1H, J = 8.2 Hz), 7.97 (s, 1H), 7.77 (s, 1H), 7.75-7.67 (m,5H), 7.19 (t, 1H, J = 8.2 Hz), 6.99 (d, 1H, J = 8.5 Hz), 3.94 (s, 3H),3.75 (t, 4H, J = 4.4 Hz), 3.05 (t, 4H, J = 4.4 Hz)

Example 11

[0277]

[0278] To the suspension of5-chloro-7-(3,4-dimethoxyphenyl)imidazo[1,2-c]pyrimidine (57.94 mg, 0.2mmol) and 4-aminobenzonitrile (35.44 mg, 0.3 mmol) in the mixture of 2.5ml 2-propanol and 1.5 ml H₂O was added conc.HCl. Then the mixture wasstirred at 85 to 90° C. overnight, and cooled to room temperature. Theproduced solid was collected by filtration and purified by preparativeTLC to give the desired product of4-[7-(3,4-dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzonitrile.(38 mg, 51.2%).

[0279] Molecular weight 371.3983

[0280] Mass spectrometry: 372

[0281] Activity grade: A

[0282] With the use of any of the intermediates I or II and according tothe procedure that is similar to that of Example11, following compoundsshown in Table 10 below were prepared. TABLE 10 Ex. No. MOLSTRUCTUREMOLWEIGHT grade MS NMR 11-1

417.4715 B (MeOD) 2.88 (3H, s), 2.90 (3H, s), 3.79 (3H, s), 3.88 (3H,s), 7.04 (1H, d, J = 8.3 Hz), 7.43-7.53 (2H, m), 7.57-7.66 (4H, m), 7.86(1H, d, J = 8.3 Hz), 7.95 (1H, d, J = 2.3 Hz), 8.16 (1H, d, J = 2.3 Hz)11-2

390.4456 A (MeOD) 2.28 (3H, s), 3.74 (3H, s), 3.82 (3H, s), 3.84 (3H,s), 6.85 (1H, dd, J = 2.9, 8.6 Hz), 6.92 (2H, m), 7.34 (2H, m),7.49-7.56 (3H, m), 7.93 (1H, s) 11-3

415.4119 A (DMSO) 3.88 (3H, s), 3.94 (3H, s), 7.17 (1H, d, J = 8.3 Hz),7.73 (1H, d, J = 7.9 Hz), 7.80 (1H, d, J = 1.9 Hz), 7.85 (1H, s), 7.86(1H, dd, J = 1.9, 8.3 Hz), 7.94 (1H, d, J = 1.5 Hz), 8.08 (1H, d, J =7.9 Hz), 8.13 (1H, m), 9.27 (1H, d, 8.3 Hz), 12.35 (1H, s), 12.28 11-4

460.5375 A (d8-DMSO) 1.11 (6H, s), 2.84 (2H, s), 3.39 (1H, m), 3.83 (3H,s), 3.85 (3H, s), 7.11 (1H, d, J = 9.0 Hz), 7.27 (2H, d, J = 8.3 Hz),7.68-7.83 (5H, m), 8.07 (1H, m), 8.75 (1H, m), 10.49 (1H, s) 11-5

444.4944 A (d8-DMSO) 1.72-1.85 (1H, m), 2.10-2.19 (1H, m), 2.42-2.58(1H, m), 2.66-2.75 (1H, m), 2.81-2.91 (2H, m), 2.93-3.01 (1H, m), 3.31(2H, m), 3.83 (3H, s), 3.85 (3H, s), 7.08 (1H, d, J = 8.2 Hz), 7.20 (1H,d, J = 8.2 Hz), 7.55-7.85 (6H, m), 8.39 (1H, s) 11-6

440.4814 C 441 11-7

360.4192 A 361 11-8

376.4185 A 377 11-9

360.4192 A (DMSO d-6) 2.31 (3H, s), 3.81 (3H, s), 3.86 (3H, s), 7.03(1H, d, J = 8.6 Hz), 7.25 (2H, d, J = 8.7 Hz), 7.60 (2H, s), 7.67-7.80(4H, m), 8.26 (1H, s), 9.45 (1H, s) 11-10

430.3898 B 431 11-11

389.4173 A (DMSO d-6) 3.81 (3H, s), 3.83 (3H, s), 7.01 (1H, d, J = 8.5Hz), 7.39 (1H, s), 7.51 (1H, t, J = 7.9 Hz), 7.63-7.65 (3H, m), 7.73(1H, s), 7.74 (1H, s), 7.99 (1H, s), 8.06 (1H, d, 7.9 Hz), 8.30 (1H, s),8.44 (1H, s), 9.67 (1H, s) 11-12

387.4042 A (DMSO d-6) 3.82 (3H, s), 3.85 (3H, s), 7.12 (1H, d, J = 8.5Hz), 7.76-7.80 (3H, m), 7.93 (1H, d, J = 8 Hz), 8.04 (1H, s), 8.13 (1H,s), 8.51 (1H, s), 8.95 (1H, s), 10.95 (1H, s) 11-13

404.432 C 405 11-14

515.5738 A 516 11-15

377.4061 A 378 11-16

346.3921 A 347 11-17

376.4185 A 377 11-18

360.4192 A 11-19

404.4291 ND 405 11-20

436.4931 A 437 11-21

432.4833 A 433 11-22

404.4291 A 405 11-23

447.4543 A 448 11-24

418.4562 A 419 (DMSO-d6) 2.58 (2H, t, J = 7.5 Hz), 2.87 (2H, t, J = 7.4Hz), 3.85 (6H, s),7.11 (1H, d, J = 8.21 Hz), 7.34 (2H, d, J = 8.2 Hz),7.70-7.80 (5H, m), 8.07 (1H, d, J = 1.4 Hz), 8.77 (1H, ), 10.51 (1H, s)11-25

390.4456 B 377 (DMSO-d6) 3.56 (3H, s), 3.58 (3H, s), 3.83 (3H, s), 3.89(3H, s), 6.28 (1H, s), 7.07 (2H, d, J = 8.5 Hz), 7.16 (1H, d, J = 8.3Hz), 7.25 (1H, d, J = 1.5 Hz), 7.29-7.32 (1H, m), 7.36-7.42 (1H, m),7.67 (1H, s), 7.79-7.84 (2H, m) 11-26

404.4291 A 405 (DMSO-d6) 3.85 (3H, s), 3.88 (6H, s), 7.14 (1H, d, J =8.5 Hz), 7.75-7.81 (3H, m), 8.06-8.13 (5H, m), 8.77 (1H, d, J = 1.6 Hz),10.71 (1H, s) 11-27

454.5085 A 455 (DMSO d-6) 3.49 (2H, t, J = 6.4Hz), 3.73 (2H, q, J = 6.4Hz), 3.82 (3H, s), 3.87 (3H, s), 7.03 (1H, d, J = 8.5 Hz), 7.64-7.79(6H, m), 8.31 (2H, s), 8.55 (1H, s), 9.88 (1H, s) 11-28

390.402 A 391 11-29

362.3914 A 363 (DMSO d-6) 3.82 (3H, s), 3.83 (3H, s), 6.85 (1H, s), 6.88(1H, s), 7.07 (1H, d, J = 9.1 Hz), 7.58-7.61 (3H, m), 7.71-7.73 (2H, m),7.88 (1H, s), 8.48 (1H, s), 9.94 (1H, s) 11-30

362.3914 A 363 (DMSOd-6) 3.85 (3H, s), 3.86 (3H, s), 6.67 (1H, d, J =7.8 Hz), 7.11 (1H, d, J = 8.6 Hz), 7.24 (1H, t, J = 8.6 Hz), 7.31 (1H,d, J = 7.8 Hz), 7.44 (1H, s), 7.71 (1H, s), 7.79 (1H, s), 8.07 (1H, s),8.91 (1H, s), 10.52 (1H, s) 11-31

362.3914 A 363 (DMSO d-6) 3.75 (3H, s), 3.77 (3H, s), 6.91 (1H, t, J =7.6 Hz), 6.96-7.00 (2H, m), 7.13 (1H, t, 7.9 Hz), 7.52 (1H, s),7.55-7.61 (4H, m), 8.23 (1H, s) 11-32

431.4986 A 432 11-33

391.3896 A 392 (DMSO d-6) 3.84 (3H, s), 3.89 (3H, s), 7.12 (1H, d, J =8.3 Hz), 7.74-7.80 (2H, m), 7.83 (1H, s), 7.90 (1H, s), 8.24 (1H, s),8.25 (2H, d, J = 9.4 Hz), 8.32 (2H, d, J = 9.4 Hz), 8.67 (1H, s), 8.88(1H, brs), 10.3 (1H. brs) 11-34

389.4609 A 390 (DMSO d-6) 3.80 (3H, s), 3.84 (3H, s), 6.82 (1H, d, J =9.2 Hz), 7.02 (1H, d, J = 8.6 Hz), 7.54 (1H, s), 7.60 (1H, s), 7.63-7.68(3H, m), 7.72 (1H, s), 8.23 (1H, s), 9.36 (1H, s) 11-35

402.4568 A 403 11-36

389.4173 A 390 11-37

376.4185 A 377 (DMSO d-6) 3.84 (6H, s), 4.58 82H, s), 7.11 (1H, d, J =8.7 Hz), 7.17 (1H, d, J = 7.9 Hz), 7.40 (1H, t, J = 7.9 Hz), 7.71-81(3H, m), 7.89 (1H, s), 8.08 (1H, s), 8.92 (1H, s), 10.28 (1H, brs),10.64 (1H, s) 11-38

422.8776 A 387 (DMSO d-6) 3.80 (3H, s), 3.85 (3H, s), 7.12 (1H, J = 8.6Hz), 7.60 (1H, d, J = 8.7 Hz), 7.75 (1H, s), 7.79-7.86 (3H, m),8.08-8.15 (3H, m), 8.84 (1H, s), 10.66 (1H, s), 13.10 (1H, brs) 11-39

382.3729 A 383 11-40

400.3634 A 401 11-41

444.8534 A 445 (DMSQ d-6) 3.83 (6H, s), 7.09 (1H, 8.7 Hz), 7.64-7.82(5H, m), 8.11 (1H, s), 8.16 (1H, q, J = 4.1 Hz), 8.34 (1H, s), 11.36(1H, brs) 11-42

404.4291 C-D 405 (DMSO d-6) 3.70 (3H, s), 3.83 (3H, s), 3.88 (3H, s),6.69 (1H, s), 7.06-7.14 (3H, m), 7.45 (1H, s), 7.78-7.83 (2H, m), 7.91(1H, s), 7.94 (1H, s) 11-43

405.4167 A 406 (DMSO d-6) 3.73 (3H, s), 3.82 (3H, s), 3.88 (3H, s),7.05-7.09 (2H, m), 7.16 (2H, d, J = 9.4 Hz), 7.58 (1H, s), 7.75-7.77(2H, m), 8.09 (1H, s), 8.19 (2H, d, J = 9.4 Hz) 11-44

396.4 A 397 11-45

394.8642 B 395 11-46

444.4169 B 445 (DMSO d-6) 3.66 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 8.59(1H, s), 7.08 (1H, d, J = 8.3 Hz), 7.25-7.28 (2H, m), 7.38-7.45 (3H, m),7.78-7.84 (2H, m), 7.88 (1H, s) 11-47

386.4574 A 387 11-48

399.4561 A 400 11-49

390.4456 B 391 11-50

394.8642 A 395 (DMSO d-6) 3.66 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 6.63(1H, s), 6.99-7.09 (2H, m), 7.31-7.43 (4H, m), 7.88-7.83 (2H, m), 7.88(1H, s) 11-51

404.4291 B 405 11-52

461.7491 A 425 (DMSO d-6) 3.82 (3H, s), 3.88 (3H, s), 7.05 (1H, d, J =8.3 Hz), 7.34 (1H, d, J = 7.9 Hz), 7.42 (1H, t, J =7.9 Hz), 7.63 (1H,s), 7.68-7.72 (3H, m), 7.87 (1H, d, J = 6.8 Hz), 8.27 (1H, s), 8.32 (1H,s), 9.65 (1H, s) 11-53

364.3825 A 365 (DMSO d-6) 3.74 (3H, s), 3.77 (3H, s), 6.96 (1H, d, J =8.3 Hz), 7.36-7.40 (3H, m), 7.53-7.62 (2H, m), 8.19 (1H, s), 9.57 (1H,s) 11-54

382.3729 A 383 (DMSO d-6) 3.75 (3H, s), 3.77 (3H, s), 6.97 (1H, d, J = 9Hz), 7.22 (1H, d, J = 7.5 Hz), 7.18-7.25 (2H, m), 7.55 (1H, s), 7.57(1H, s), 7.72 (1H, d, J = 7.7 Hz), 8.15 (1H, s), 9.58 (1H, s) 11-55

380.8371 A 381 (DMSO d-6) 3.71 (3H, s), 3.76 (3H, s), 6.95 (1H, d, J =8.3 Hz), 7.38 (1H, d, J = 7.8 Hz), 7.37-7.51 (2H, m), 7.56 (1H, s), 7.62(1H, s), 7.73 (1h, d, J = 7.9 Hz), 8.18 (1H, s), 9.59 (1H, brs) 11-56

391.3896 A 392 (DMSO d-6) 3.83 (3H, s), 3.88 (3H, s), 6.97 (1H, J = 8.3Hz), 7.50 (2H, s), 7.66 (2H, s), 7.69 ( 1H, s), 7.753 (1H, s), 8.03 (2H,s), 8.25 (1H, s), 10.17 (1H, brs) 11-57

382.3729 A 383 (DMSO d-6) 3.82 (3H, s), 3.87 (3H, s), 7.05 (1H, d, J =8.3 Hz), 7.49-7.73 (6H, m), 8.12-8.24 (2H, m), 9.71 (1H, s) 11-58

412.8795 A 377 (DMSO d-6) 3.81 (3H, s), 3.85 (3H, s), 3.86 (3H, s), 6.83(1H, d, J = 8.7 Hz), 7.12 (1H, J = 8.3 Hz), 7.37-7.46 (2H, m), 7.62 (1H,s), 7.73-7.77 (3H, m), 8.08 (1H, s), 10.48 (1H, s) 11-59

388.4297 A 389 (DMSO d-6) 2.63 (3H, s), 3.82 (3H, s), 3.83 (3H, s), 7.03(1H, d, J = 8.7 Hz), 7.63-7.78 (6H, m), 822 (1H, d, J = 6.2 Hz), 8.29(1H, s), 8.50 (1H, s), 9.72 (1H, s) 11-60

364.3825 A 365 (DMSO d-6) 3.81 (3H, s), 3.85 (3H, s), 7.03 (1H, d, J =8.7 Hz), 7.26-7.32 (2H, m), 7.62 (2H, s), 7.65-7.71 (2H, m), 7.87-7.92(2H, m), 8.24 (s, 1H), 9.57 (1H, s) 11-61

380.8371 A 381 (DMSO d-6) 3.81 (3H, s), 3.86 (3H, s), 7.05 (1H, d, J =8.3 Hz), 7.50 (2H, d, J = 9 Hz), 7.62-7.72 (4H, m), 7.94 (2H, d, J = 9Hz), 8.25 (1H, s) 11-62

434.3287 A 362 (DMSO d-6) 3.85 (3H, s), 3.86 (3H, s), 7.11 (1H, d, J =8.5 Hz), 7.37 (2H, d, J = 8.7 Hz), 7.72-7.77 (2H, m), 7.94 (2H, d, J =8.7 Hz), 8.10 (1H, s), 8.92 (1H, s), 10.85 (1H, s) 11-63

385.429 A 386 (DMSO d-6) 3.81 (3H, s), 3.86 (3H, s), 4.05 (2H, s), 7.05(1H, d, J = 8.4 Hz), 7.42 (2H, d, J = 8.5 Hz), 7.62-7.73 (4H, m), 7.92(2H, d, 8.5 Hz), 8.28 (1H, s), 9.61 (1H, s) 11-64

389.4173 A 390 (DMSO d-6) 3.86 (3H, s), 3.89 (3H, s), 7.13 (1H, d, J =8.5 Hz), 7.30 (1H, t, J = 7.6 Hz), 7.72-7.82 (4H, m), 7.97-8.04 (3H, m),8.14 (1H, s), 8.55 (1H, s), 8.72 (1H, d, J = 8.3 Hz), 13.16 (1H, s)11-65

406.445 A 407 3.74 (3H, s), 3.77 (3H, s), 3.78 (3H, s), 3.81 (3H, s),6.63 (1H, d, J = 8.6 Hz), 6.74 (1H, d, J = 2.6 Hz), 6.95 (1H, d, J = 8.3Hz), 7.50-7.57 (5H, m), 8.18 (1H, s), 8.98 (1H, s) 11-66

388.4326 A 389 (DMSO d-6) 3.94 (3H, s), 3.97 (3H, s), 6.98 (1H, d, J =8.9 Hz), 7.36 (1H, d, J = 8.7 Hz), 7.46 (1H, s), 7.58-7.63 (3H, m), 8.15(1H, s), 8.47 (1H, d, J = 8.7 Hz), 8.93 (1H, s), 9.50 (1H, s) 11-67

461.3545 A 389 (DMSO d-6) 3.86 (3H, s), 3.90 (3H, s), 7.12 (1H, J = 8.5Hz), 7.75-7.83 (3H, m), 7.98 (2H, d, J = 8.7 Hz), 8.09 (1H, s), 829 (2H,8.7 Hz), 9.05 (1H, s), 9.12 (1H, s), 9.34 (2H, s), 11.20 (1H, s) 11-68

506.4365 A 434 11-69

430.3899 A 431 (DMSO d-6) 3.82 (3H, s), 3.87 (3H, s), 7.03 (1H, d, J =8.3 Hz), 7.14 (1H, d, J = 7.2 Hz), 7.57 (1H, t, J = 8.3 Hz), 7.64 (1H,s), 7.69-7.72 (3H, m), 7.90 (1H, d, J = 7.2 Hz), 8.13 (1H, s), 8.29 (1H,s), 9.76 (1H, s) 11-70

427.8506 A 392 11-71

414.3905 A 415 (DMSO d-6) 3.82 (3H, s), 3.87 (3H, s), 7.07 (1H, d, J = 9Hz), 7.64 (1H, s), 7.71-7.73 (3H, m), 7.80 (2H, d, J = 8.7 Hz), 8.16(2H, d, J = 8.7 Hz), 8.30 (1H, s), 9.89 (1H, brs) 11-72

439.9054 A 404 11-73

481.5779 A 482 (DMSO d-6) 0.78 (3H, t, J = 7.5 Hz), 1.22 (2H, h, J = 7.5Hz), 2.79 (2H, q, J = 6 Hz), 3.81 (3H, s), 3.87 (3H, s), 7.01 (1H, d, J= 8.7 Hz), 7.53-7.56 (2H, m), 7.64-7.70 (4H, m), 7.77 (1H, d, J = 8.5Hz), 8.22 (1H, d, J = 8.5 Hz), 8.30 (1H, s), 8.44 (1H, 11-74

541.9079 A 433 (DD3OD) 2.97 (6H, s), 3.43 (2H, t, J = 6.0), 3.62 (2H, t,J = 6.0), 3.87 (3H, s), 3.90 (3H, s), 6.96 (2H, d, J = 8.7), 7.06 (1H,d, J = 8.1), 7.57 (1H, s), 7.64 (2H, d, J = 8.7), 7.72-7.77 (2H, m),7.93 (1H, d, J =2.1), 8.33 (1H, s) 11-75

456.8839 A 421 (DMSO-d6) 3.81 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 7.08(1H, d, J =8.4), 7.35 (1H, dd, J = 3.0 and 8.7), 7.53 (1H, d, J = 3.0),7.63-7.71 (3H, m), 7.98 (1H, d, J = 8.7), 8.11 (1H, d, J = 1.8), 8.36(1H, d, J = 1.8), 11.06 (1H, s) 11-76

461.928 A 426 (DMSO-d6) 3.85 (3H, s), 3.87 (3H, s), 7.14 (1H, d, J =8.4), 7.37 (2H, s(br)), 7.73-8.97 (3H, m), 7.93 (2H, d, J = 8.4),8.10-8.15 (3H, m), 8.97 (1H, s), 11.02 (1H, s) 11-77

390.3972 A 391 11-78

551.7661 A (DMSO d-6) 3.86 (3H, s), 3.90 (3H, s), 7.13 (1H, d, J = 8.6Hz), 7.72 (1H, s), 7.79-7.81 (2H, m), 7.97 (1H, s), 8.04-8.10 (3H, m),8.33 (1H, s), 8.52 (1H, d, J = 8.7 Kz), 8.59 (1H, brs), 12.95 (1H, brs)11-79

515.5671 A 516 11-80

497.9366 A 11-81

425.9176 A (DMSO) 3.83 (3H, s), 3.85 (3H, s), 4.29-4.51 (6H, broad s),6.75 (1H, s), 7.12 (1H, d, J = 8.4 Hz), 7.33 (3H, s), 7.73 (2H, m), 7.80(1H, d, J = 8.4 Hz), 8.11 (1H, d, J = 1.4 Hz), 8.78 (1H, s), 10.44 (1H,s) 11-82

511.0229 A (DMSO) 3.30 (6H, m), 3.53 (2H, t, J = 6.1 Hz), 3.84 (3H, s),3.85 (3H, s), 3.91 (4H, m), 6.79 (2H, AB, J = 8.9 Hz), 7.10 (1H, d, J =8.9 Hz), 7.58 (2H, AB, J = 8.9 Hz), 7.62 (1H, s), 7.73 (1H, s), 7.76(1H, m), 8.09 (1H, d, J = 2.3 Hz), 8.75 (1H, d, J = 2.3 Hz), 10.41 (1H,s) 11-83

555.0319 B (DMSO) 3.46 (4H, broad s), 3.81 (3H, s), 3.83 (4H, m), 3.84(3H, s), 3.90 (3H, s), 4.17 (2H, broad s), 7.10 (1H, d, J = 8.5 Hz),7.22 (1H, d, J = 9.0 Hz), 7.68 (3H, m), 7.80 (1H, dd, J = 2.0, 8.5 Hz),8.08 (1H, d, J = 2.0 Hz), 8.43 (1H, s), 8.85 (1H, s), 10.05 (1H, s),10.66 (1H, s) 11-84

442.906 A 407 (CD3OD) 3.85 (3H, s), 3.87 (3H, s), 3.88 (3H, s), 3.90(3H, s), 7.06 (1H, dd, J = 3.6 and 8.4), 7.31 (1H, dd, J = 2.4 and 8.4),7.43 (1H, d, J =2.4), 7.56 (1H, s), 7.74-7.79 (2H, m), 7.92 (1H, d, J =2.1), 8.29 (1H, d, J = 1.8) 11-85

505.759 A 469 (DMSO-d6) 3.84 (3H, s), 3.85 (3H, s), 7.11 (1H, d, J =8.4), 7.67 (1H, d, J = 1.8), 7.72-7.78 (2H, m), 7.97 (1H, dd, J = 2.4and 8.7), 8.13 (2H, dd, J = 2.1 and 13.2), 8.24-8.30 (2H, m), 11.68 (1H,s) 11-86

519.7861 A 485 (DMSO-d6) 3.61 (3H, s), 3.82 (3H, s), 3.83 (3H, s), 7.08(1H, d, J =8.4), 7.60 (1H, d, J = 1.8), 7.68 (1H, dd, J = 2.1 and 8.7),7.76 (1H, s), 7.98-8.10 (4H, m), 8.35 (1H, s), 10.87 (1H, s) 11-87

479.7395 A 445 (CD3OD) 3.81 (3H, s), 3.88 (3H, s), 7.32 (1H, d, J =8.4), 7.51 (1H, m), 7.53-7.60 (2H, m), 7.61-7.71 (2H, m), 7.99 (1H, d, J= 2.4), 8.28 (1H, d, J = 2.1) 11-88

496.1941 A 461 (CD3OD) 3.79 (3H, s), 3.85 (3H, s), 6.98 (1H, d, J =9.0), 7.42 (1H, s), 7.53-7.61 (4H, m), 7.71-7.79 (2H, m), 7.99 (1H, s)11-89

438.877 A 403 (DMSO) 3.81 (3H, s), 3.84 (3H, s), 7.02 (1H, d, J = 8.4Hz), 7.11 (1H, d, J = 8.4 Hz), 7.33 (1H, dd, J = 1.9, 8.4 Hz), 7.49 (1H, d, J+321 .6 Hz), 7.67 (1H, s), 7.71 (1H, d, J = 1.9 Hz), 7.76 (1H,dd, J = 1.9, 8.4 Hz), 8.06 (1H, d, J = 2.1 Hz), 8.62 (1H, d, J = 1.9Hz), 10.29 (1H, s), 10.65 (1H, s), 10.73 (1H, s) 11-90

525.0554 A 489 (DMSO) 2.04 (2H, quint., J = 7.7 Hz), 3.20 (6H, m), 3.84(3H, s), 3.85 (3H, s), 3.90 (6H, m), 6.83 (2H, d, J = 7.4 Hz), 7.11 (1H,d, J = 9.0 Hz), 7.62 (3H, m), 7.75 (2H, m), 8.08 (1H, d, J = 2.2 Hz),8.81 (1H, d, J = 2.2 Hz), 10.48 (1H, s) 11-91

475.5522 A 476 (DMSO d-6) 2.58 (4H, t, J = 4.4 Hz), 2.81 (2H, t, J = 5.6Hz), 3.74 (4H, t, J = 4.4Hz), 3.91 (6H, s), 4.11 (2H, t, J = 5.6 Hz),6.90-6.94 (3H, m), 7.40 (1H, s), 7.54-7.68 (6H, m), 7.87 (1H, s) 11-92

428.8789 A 393 (CD3OD) 3.90 (9H, s(br)), 6.99-7.13 (3H, m), 7.43 (1H, d,J = 2.4), 7.56 (1H, s), 7.74 (1H, dd, J = 1.8 and 6.3), 7.85 (1H, d, J =1.8), 7.93 (1H, d, J = 2.1), 8.31 (1H, s) 11-93

428.8789 A 393 (CD3OD) 3.78 (3H, s), 3.80 (3H, s), 3.87 (3H, s),6.57-6.59 (2H, m), 7.02 (1H, d, J = 8.4), 7.42 (1H, d, J =8.4), 7.49(1H, s), 7.64-7.67 (m, 2H), 7.87 (1H, d, J = 2.1), 8.20 (2H, d, J = 1.5)11-94

418.4998 C 419 (CDCl3) 1.00 (3H, t, J = 7.4 Hz), 1.48-1.58 (2H, m), 1.80(2H, quint., J = 6.5 Hz), 3.93 (3H, s), 3.95 (3H, s), 3.99 (2H, t, J =6.5 Hz), 6.55 (1H, s), 6.91-6.98 (3H, m), 7.37 (1H, s), 7.48 (1H, s),7.57-7.61 (3H, m), 7.64 (1H, d, J = 1.5 Hz), 7.68 (1H, d, J = 2.0 Hz)11-95

430.3899 A 431 (CDCl3) 3.94 (6H, s), 6.76 (1H, s), 6.97 (1H, d, J = 8.4Hz), 7.29 (1H, AB, J = 8.9 Hz), 7.46 (1H, s), 7.54 (1H, s), 7.60 (1H,dd, J = 2.0, 8.4 Hz), 7.65 (1H, d, J = 2.0 Hz), 7.69 (1H, d, J = 1.4Hz), 7.79 (2H, AB, J = 8.9 Hz) 11-96

455.9048 A 420 (MeOD) 3.90 (3H, s), 3.92 (6H, s), 7.09 (1H, d, J = 8.2Hz), 7.22 (1H, dd, J = 2.9, 9.2 Hz), 7.48 (1H, d, J = 2.9 Hz), 7.58 (1H,s), 7.75 (1H, s), 7.76 (1H, m), 7.96 (2H, m), 8.68 (1H, d, J = 9.2 Hz)11-97

504.7743 A 468, 469 (DMSO) 3.85 (3H, s), 3.90 (3H, s), 7.13 (1H, d, J =8.5 Hz), 7.73 (1H, s), 7.80 (2H, m), 7.90-7.95 (2H, m), 8.07 (2H, s),8.20 (1H, s), 8.59 (1H, s), 8.70 (1H, d, J = 8.9 Hz), 12.9 (1H, s) 11-98

404.4727 A 405 (DMSO) 1.29 (6H, d, J = 6.0 Hz), 3.80 (3H, s), 3.83 (3H,s), 4.61 (1H, sept., J = 6.0 Hz), 7.00 (2H, AB, J = 8.9 Hz), 7.03 (1H,m), 7.58 (2H, AB, J = 8.9 Hz), 7.67 (1H, dd, J = 1.9, 8.4 Hz), 7.74 (3H,m), 8.22 (1H, s), 9.39 (1H, s) 11-99

439.9054 A 404 (MeOD) 2.93 (3H, s), 3.85 (3H, s), 3.90 (3H, s), 6.99(1H, d, J = 7.4 Hz), 7.20 (1H, t, J = 6.9 Hz), 7.47-7.54 (2H, m),7.61-7.66 (2H, m), 7.81 (1H, d, J = 7.7 Hz), 7.85 (1H, s), 7.95 (1H, s),8.73 (1H, d, J = 7.7 Hz) 11-100

394.409 A 395 (DMSO) 3.81 (3H, s), 3.86 (3H, s), 3.86 (3H, s), 7.05 (1H,d, J = 8.5 Hz), 7.24 (1H, t, J = 9.3 Hz), 7.54 (1H, d, J = 8.9 Hz), 7.61(2H, s), 7.68 (1H, dd, J = 1.9, 8.5 Hz), 7.74 (1H, d, J = 1.9 Hz), 7.99(1H, dd, J = 2.5, 13.9 Hz), 8.23 (1H, s), 9.54 (1H, s) 11-101

535.3856 A (DMSO d-6) 2.63 (2H, t, J = 4.7 Hz), 2.88 (2H, t, J = 7.7Hz), 3.85 (3H, s), 3.92 (3H, s), 7.12 (1H, d, J = 9 Hz), 7.55 (1H, d, J= 8.7 Hz), 7.72 (1H, brs), 7.81-7.84 (3H, m), 7.88 (1H, s), 8.33 (1H,brs), 8.56 (1H, s), 8.96 (1H, s, 8.6 Hz) 11-102

463.323 A (DMSO d-6) 3.85 (3H, s), 3.92 (3H, s), 7.12 (1H, d, J = 9 Hz),7.22 (1H, t, J = 7.3 Hz), 7.66 (1H, t, J = 7.3 Hz), 7.75 (1H, brs),7.82-7.85 (2H, m), 7.90-7.95 (2H, m), 8.36 (1H, brs), 8.58 (1H, s), 9.07(1H, d, 8.2 Hz) 11-103

496.784 A (DMSO d-6) 3.84 (3H, s), 3.86 (3H, s), 7.10 (1H, d, J = 8.4Hz), 7.70 (1H, d, J = 8.7 Hz), 7.76-7.86 (4H, m), 8.05 (1H, s), 8.33(1H, s), 8.63 (1H, s), 10.30 (1H, s) 11-104

483.4578 A (DMSO d-6) 2.64 (2H, t, J = 7.8 Hz), 2.89 (2H, t, J = 4.8Hz), 3.85 (3H, s), 3.90 (3H, s), 7.12 (1H, d, J = 8.3 Hz), 7.57 (1H, d,J = 8.6 Hz), 7.73-7.80 (3H, m), 7.87-7.94 (4H, m), 8.48 (1H, s), 8.75(1H, d, J = 8.5 Hz) 11-105

475.5025 A (DMSO d-6) 1.89 (2H, p, J = 7.4 Hz), 2.27 (2H, t, J = 4.4Hz), 2.65 (2H, t, J = 7.4 Hz), 3.83 (3H, s), 3.90 (3H, s), 7.08 (1H, d,J = 8.5 Hz), 7.51 (1H, d, J = 7.0 Hz), 7.68-7.78 (5H, m), 7.83 (1H, s),7.91 (1H, s), 8.49 (1H, s), 8.93 (1H, d, J = 6.8 Hz), 12.06 (1H, brs),11-106

549.4124 A 11-107

497.4846 A 11-108

498.4727 A (DMSO d-6) 1.81 (2H, p, J = 7.3 Hz), 2.02 (2H, t, J = 7.3Hz), 2.58 (2H, t, J = 7.3 Hz), 3.83 (3H, s), 3.90 (3H, s), 7.09 (1H, d,J = 8.3 Hz), 7.36-7.67 (3H, m), 7.79-7.83 (3H, m), 8.39 (1H, brs), 8.87(1H, d, J = 8.5 Hz) 11-109

434.4102 A (DMSO d-6) 3.86 (3H, a), 3.87 (3H, s), 7.11 (1H, d, J = 8.8Hz), 7.71 (1H, s), 7.85-7.88 (2H, m), 7.90 (1H, s), 7.98 (1H, s),8.11-8.12 (2H, m), 8.23-8.26 (2H, m), 8.82 (1H, s), 13.10 (1H, brs)11-110

503.9688 A (DMSO-d6) 3.85 (3H, s), 3.86 (3H, s), 6.74 (4H, m(br)), 7.14(1H, d, J =8.4), 7.74-7.87 (5H, m), 7.99-8.07 (2H, m), 8.07 (1H, d, J =2.1), 8.67 (1H, d, J = 1.8), 10.63 (1H, s) 11-111

504.5878 C (CDCl3) 2.45 (4H, t, J = 4.6 Hz), 2.65 (2H, t, J = 6.1 Hz),3.19 (2H, t, J = 6.1 Hz), 3.70 (4H, t, J = 4.6 Hz), 3.89 (3H, s), 3.92(3H, s), 3.93 (3H, s), 4.84 (1H, s), 6.78 (2H, m), 6.91 (1H, d, J = 2.6Hz), 6.95 (2H, m), 7.41 (1H, s), 7.45 (1H, s), 7.61 (1H, d, J = 1.3 Hz),7.63 (1H, d, J = 2.0 Hz), 7.66 (1H, s) 11-112

492.5768 B (CDCl3) 2.31 (3H, s), 2.59 (2H, t, J = 5.3 Hz), 2.70 (2H, t,J = 6.1 Hz), 3.26 (2H, t, J = 6.1 Hz), 3.63 (2H, t, J = 5.3 Hz), 3.87(3H, s), 3.93 (3H, s), 3.94 (3H, s), 6.76 (1H, d, J = 8.5 Hz), 6.92 (1H,s), 6.95 (1H, m), 7.02 (1H, s), 7.09 (1H, dd, J = 2.4, 8.5 Hz), 11-113

461.928 A (CD3OD) 3.98 (3H, s), 4.02 (s, 3H), 7.20 (1H, d, J = 8.5),7.59 (1H, t, J =7.5), 7.79-7.88 (4H, m), 8.08 (1H, d, J = 2.0),8.16-8.22 (2H, m), 8.59 (1H, d, J = 8.0) 11-114

461.928 A (DMSO-d6) 3.85 (3H, s), 3.86 (3H, s), 7.09 (1H, d, J = 8.5),7.44 (2H, s), 7.70 (3H, d, J = 5.0), 7.78-7.84 (2H, m), 8.06-8.15 (2H,m), 8.38 (1H, s), 8.65 (1H, s), 10.58 (1H, s) 11-115

516.0194 A (DMSO-d6) 1.66-1.69 (4H, m), 3.17-3.18 (4H, m), 3.85 (3H, s),3.87 (3H, s), 7.14 (1H, d, J = 8.5), 7.75-7.82 (3H, m), 7.93 (2H, d, J=8.5), 8.07 (1H, d, J = 2.0), 8.18 (2H, d, J = 8.5), 8.76 (1H, s), 10.79(1H, 11-116

532.0184 A (DMSO-d6) 2.91 (4H, t(br), J = 4.5), 3.66 (4H, t(br), J =4.5), 7.15 (1H, d, J = 8.5), 7.76-7.88 (5H, m), 8.11-8.22 (3H, m),8.76-8.79 (1H, s(br)), 10.86-10.98 (1H, s(br)) 11-117

466.9267 A (DMSO) 3.37 (3H, s), 3.38 (3H, s), 3.80 (3H, s), 3.83 (3H,s), 7.11 (1H, d, J = 8.3 Hz), 7.26 (1H, d, J = 8.3 Hz), 7.51 (1H, dd, J= 1.9, 8.3 Hz), 7.63 (1H, d, J = 1.5 Hz), 7.68 (1H, d, J = 1.9 Hz), 7.70(1H, s), 7.77 (1H, dd, J = 1.9, 8.3 Hz), 8.08 (1H, d, J = 1.9 Hz) 11-118

452.8999 A (DMSO) 3.32 (3H, s), 3.81 (3H, s), 3.84 (3H, s), 7.10 (1H, d,J = 8.3 Hz), 7.18 (1H, d, J = 8.3 Hz), 7.42 (1H, dd, J = 1.9, 8.3 Hz),7.56 (1H, d, J = 1.9 Hz), 7.68 (1H, s), 7.71 (1H, d, J = 1.9 Hz), 7.76(1H, dd, J = 1.9, 8.3 Hz), 8.07 (1H, d, J = 1.9 Hz), 8.64 (1H, d, 11-119

424.479 A (DMSO d-6) 3.82 (6H, s), 7.01 (1H, d, J = 9.0 Hz), 7.50 (1H,br), 7.58-7.75 (4H, m), 7.88 (2H, s), 8.02 (1H, d, J = 7.6 Hz), 8.43(1H, d, J =7.9 Hz), 9.73 (1H, br) 11-120

424.479 A (DMSO d-6) 3.25 (3H, s), 3.82 (3H, s), 3.87 (3H, s), 7.02 (1H,d, J = 8.6 Hz), 7.64-7.79 (5H, m), 8.28-8.30 (3H, m), 8.57 (1H, br),9.88 (1H, br) 11-121

407.8592 B (CDCl3) 3.74 (3H, s), 3.81 (3H, s), 7.08 (1H, d, J = 8.5 Hz),7.54-7.58 (2H, m), 7.63-7.65 (1H, m), 7.75-7.78 (2H, m), 7.87-7.90 (1H,m), 8.04 (1H, d, J = 7.9 Hz), 8.09 (1H, s), 8.51 (1H, s), 10.94 (1H,bs). 11-122

439.4939 A (DMSO) 3.57 (3H, s), 3.80 (3H, s), 3.82 (3H, s), 7.03 (1H, d,J = 8.1 Hz), 7.40 (1H, s), 7.66 (3H, m), 7.72 (1H, s), 7.80 (3H, s),7.90 (1H, d, J = 5.4 Hz), 8.57 (1H, d, J = 8.1 Hz), 9.46 (1H, s) 11-123

453.5207 A (DMSO d-6) 2.58 (6H, s), 3.78 (3H, s), 3.79 (3H, s), 7.00(1H, d, J = 9.0 Hz), 7.45-7.50 (1H, m), 8.43 (1H, d, J = 8.3 Hz), 9.61(1H, br) 11-124

397.864 A 11-125

460.5312 B (DMSO d-6) 1.76-1.86 (2H, m), 2.27 (2H, t, 7.5 Hz), 2.62 (2H,t, J =7.5 Hz), 3.62 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 6.40 (1H, s),7.06-7.11 (3H, m), 7.24-7.26 (2H, m), 7.32 (1H, d, J = 1.5 Hz),7.78-7.85 (3H, m), 12.04 (1H, br) 11-126

474.558 10000 (DMSO d-6) 1.35 (3H, t, J = 4.2 Hz), 1.78-1.85 (2H, m),2.20-2.28 (2H, m), 3.82 (3H, s), 3.88 (3H, s), 4.11-4.18 (2H, m), 6.31(1H, s), 7.08-7.10 (3H, m), 7.25-7.26 (2H, m), 7.30 (1H, s), 7.76 (1H,s), 7.79-7.82 (2H, m), 12.00 (1H, br) 11-127

424.479 A (DMSO), 3.22 (3H, s), 3.82 (3H, s), 3.88 (3H, s), 7.08 (1H, d,J = 9.0 Hz), 7.23 (1H, s), 7.65 (1H, d, J = 1.5 Hz), 7.74 (2H, s), 7.98(2H, d, J = 8.7 Hz), 8.21 (2H, d, J = 8.7 Hz), 8.30 (1H, s), 9.94 (1H,s) 11-128

432.4816 A (DMSOd-6) 3.11 (36H, s), 3.83 (3H, s), 3.88 (3H, s), 6.47(1H, d, J = 9 Hz), 7.05 (1H, d, J = 8.5 Hz), 7.52 (1H, brs), 7.69-7.84(6H, m), 8.18 (1H, brs), 8.47 (1H, s) 11-129

404.432 A 405

Example 12

[0283]

[0284] To the solution of m-fluoroaniline (88.90 mg, 0.8 mmol) in 1.5 mlof dry DMSO was added, potassium tert-butoxide (94.26 mg, 0.84 mmol),and 5-ethylsulfenyl-7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidin(126.16 mg, 0.4 mmol). The resulting solution was stirred overnight and3 ml of ice water was added. The produced precipitate was collected byfiltration, and washed with water, 2-propanol, and ether to give crudeproduct of(3-fluorophenyl)-[7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidin-5-yl]amine.The crude product was purified by preparative TLC to give the pureproduct (127.000 mg, 87.1%).

[0285] Mass spectrometry: 365

[0286] Activity grade: A

[0287] With the use of any of the intermediates I or II and according tothe procedure that is similar to that of Example 12, following compoundsshown in Table 11 below were prepared. TABLE 11 Ex. Activity No.MOLSTRUCTURE MOLWEIGHT grade MS NMR 12-1

459.5527 B (CDCl3) 2.54 (4H, bs), 2.59-2.64 (2H, m), 2.79-2.87 (2H, m),3.68-3.77 (4H, m) 3.94 (3H, S), 3.97 (3H, s), 6.78 (1 H, bs), 6.95 (1H,d, J = 7.5 Hz), 7.22-7.28 (3H, m), 7.45 (1H, s), 7.49 (1H, s), 7.59-7.62(1H, m), 7.65-7.71 (4H, m) 12-2

386.4166 A 387 12-3

347.3796 A 348 12-4

377.4061 A (DMSO d-6) 3.80 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 6.94(1H, d, J = 8.9 Hz), 7.02 (1H, d, 8.5 Hz), 7.61-7.68 (4H, m), 8.17 (1H,s), 8.19 (1H, s), 8.56 (1H, s), 9.59 (1H, s) 12-5

410.4549 B 411 12-6

447.5195 B 448 12-7

347.3796 A 348 12-8

347.3796 A (DMSO d-6) 3.83 (3H, s), 3.89 (3H, s), 7.08 (1H, d, J = 8.2Hz), 7.65 (1H, s), 7.73-7.76 (3H, m), 7.97 (2H, d, J = 5.9 Hz), 8.29(1H, s), 8.53 (2H, d, J = 5.9 Hz), 9.95 (1H, brs) 12-9

426.2757 A (DMSO d-6) 3.82 (3H, s), 3.88 (3H, s), 7.06 (1H, s, J = 8.6Hz), 7.57 (1H, s), 7.65 (1H, s), 7.68 (1H, s), 7.70 (1H, s), 8.09 (1H,d, J = 9.0 Hz), 8.35 (2H, m), 8.51 (1H, s), 10.64 (1H, brs) 12-10

332.365 A (DMSO d-6) d 3.85 (3H, s), 7.07 (1H, d, J = 8.6 Hz), 7.27 (1H,m), 7.49-7.64 (5H, m), 7.81 (1H, s), 7.83 (1H, s), 8.06 (1H, d, J = 2.2Hz), 8.49 (1H, d, J = 1.9 Hz), 9.30 (1H, broad s), 10.15 (1H, s). 12-11

380.8371 A 12-12

425.2881 A 425 12-13

414.3905 B 415 12-14

436.4716 A 12-15

377.4061 A (CDCl3) d 3.95 (3H, s), 3.98 (3H, s), 6.97 (3H, d, J = 9Hz),7.47(1H, s), 7.65 (1H, dd, J = 2 Hz, 8.4 Hz), 7.72 (1H, d, J = 2 Hz),7.78 (2H, d, J = 9 Hz), 7.99 (1H, s), 8.29 (1H, s) 12-16

459.5471 A 460 (CDCl3) d 2.05 (2H, quint, J = 6.8 Hz), 2.48 (4H, t, J =4.4 Hz), 2.56 (2H, t, J = 7.1 Hz), 3.73 (4H, t, J =4.6 Hz), 3.94 (3H,s), 4.16 (2H, t, J =6.6 Hz), 6.76 (1H, s), 6.98 (1H, d, J = 8.4 Hz),7.20 (1H, t, J = 7.4 Hz), 7.39-7.46 (3H, m), 7.51 (1H, s), 12-17

374.3982 A 375 (CDCl3) d 2.37 (3H, s), 3.87 (3H, s), 6.93 (1H, s), 6.98(1H, d, J = 8.7 Hz), 7.18 (1H, t, J = 7.4 Hz), 7.25-7.45 (4H, m),7.61-7.71 (4H, m), 7.87 (1H, dd, J = 2.2, 8.6 Hz). 12-18

422.4858 B 423 (DMSO d-6) d 3.94 (3H, s), 5.22 (2H, s), 6.85 (1H, s),6.95 (1H, d, J =8.3 Hz), 7.19 (1H, t, J = 7.4 Hz), 7.28-7.55 (8H, m),7.65 (1H, d, J =1.5 Hz), 7.72-7.76 (3H, m). 12-19

332.3614 A 333 (DMSO d-6) d 3.86 (3H, s), 6.84 (1H, d, J = 8.3 Hz), 7.15(1H, t, J =7.3 Hz), 7.45 (2H, m), 7.55-7.60 (3H, m), 7.33 (1H, d, J =1.9 Hz), 7.91 (1H, d, J = 7.7 Hz), 8.26 (1H, s), 9.25 (1H, s), 9.50 (1H,s). 12-20

404.4676 A 405 (CDCl3) d 1.24 (3H, t, J =7.0 Hz), 3.61 (H, q, J = 7.0Hz), 3.85 (2H, t, J = 5.3 Hz), 4.24 (2H, t, J = 5.3 Hz), 6.68 (1H, s),6.99 (1H, d, J = 8.4 Hz), 7.20 (1H, t, J = 7.5 Hz), 7.40-7.45 (3H, m),7.52 (1H, s), 7.58 (1H, dd, J = 2.1, 8.4 Hz), 7.60-7.76 (4H, m). 12-21

344.3724 B 345 (CDCl3) d 4.30 (3H, s), 6.93 (1H, d, J = 8.4 Hz), 7.04(1H, broad s), 7.19 (1H, t, J = 7.4 Hz), 7.44 (3H, m), 7.52-7.64 (4H,m), 7.73 (2H, d, J = 7.8 Hz). 12-22

330.3456 B 331 (CDCl3) d 6.00 (2H, s), 6.70(1H, broad s), 6.89 (1H, d, J= 8.2 Hz), 7.21 (1H, t, J = 7.4 Hz), 7.42-7.48 (4H, m), 7.52 (1H, d, J =1.7 Hz), 7.58 (1H, dd, J = 1.7, 8.2 Hz), 7.66. 7.71 (3H, m). 12-23

374.4418 A 375 (CDCl3) d 1.47 (6H, t, J = 7.0 Hz), 1.49 (3H, t, J = 7.0Hz), 4.17 (4H, m), 6.95 (1H, d, J = 8.4 Hz), 7.18 (1H, t, J = 7.4 Hz),7.38-7.48 (4H, m), 7.55-7.71 (4H, m), 7.79 (2H, d, J = 8.0 Hz). 12-24

462.547 B 463 (CDCl3) d 1.24 (6H, t, J = 7.0 Hz), 3.62 (4H, m), 3.84(4H, q, J = 5.1 Hz), 4.23 (4H, m), 6.75 (1H, s), 6.99 (1H, d, J = 8.5Hz), 7.19(1H, t, J = 7.4 Hz), 7.40-7.49 (4H, m), 7.60 (1H, dd, J = 2.1,8.4 Hz), 7.65 (1H, d, J = 21.3 Hz), 7.72-7.75 (3H, m). 12-25

445.5203 A 446 (CDCl3) d 2.59 (4H, t, J = 4.6 Hz), 2.87 (2H, t, J = 6.1Hz), 3.73 (4H, t, J = 4.6 Hz), 3.90 (3H, s), 4.23 (2H, t, J = 6.1 Hz),6.95 (1H, d, J = 8.5 Hz), 7.18 (2H, s), 7.39-7.76 (9H, m). 12-26

445.5203 A 446 (CDCl3) d 2.61 (4H, t, J = 4.6 Hz), 2.87 (2H, t, J = 6.0Hz), 3.74 (4H, t, J = 4.6 Hz), 3.93 (3H, s), 4.22 (2H, t, J = 6.0 Hz),6.83 (1H, s), 6.97 (1H, d, J = 8.5 Hz), 7.19 (1H, t, J =7.4 Hz),7.39-7.76 (9H, m). 12-27

422.4858 C 423 (CDCl3) d 3.94 (3H, s), 5.21 (2H, s), 6.72 (1H, broad s),6.98 (1H, d, J = 8.6 Hz), 725-7.44 (10H, m), 7.64 (2H, m), 7.72 (3H, m).12-28

404.4676 A 405 (CDCl3) d 1.24 (3H, t, J = 7.0 Hz), 3.62 (2H, q, J = 7.0Hz), 3.87 (2H, t, J = 5.3 Hz), 4.27 (2H, t, J = 5.3 Hz), 6.70 (1H, s),6.95 (1H, d, J =8.5 Hz), 7.20 (1H, t, J = 7.4 Hz), 7.32-7.50 (4H, m),7.60-7.75 (5H, m) 12-29

362.3912 A 363 12-30

381.8214 A 382 12-31

354.393 B 355 12-32

361.3595 A (d8-DMSO) 3.99 (3H, s), 7.12-7.22 (1H, m), 7.38-7.50 (3H, m),7.65 (1H, s), 7.75 (1H, s), 7.85 (2H, d, J = 7.9 Hz), 8.31 (1H, s), 8.40(1H, J = 2.3 Hz), 9.63 (1H, s) 12-33

374.3982 A (CDCl3) d 2.41 (3H, s), 3.65 (3H, s), 6.84 (1H, d, J = 8.3Hz), 7.12-7.21 (3H, m), 7.28-7.43 (4H, m), 7.60 (2H, m), 7.74 (2H, d, J= 7.7 Hz). 12-34

475.6141 A (CDCl3) d 2.02 (2H, quint, J = 6.8 Hz), 2.57 (2H, t, J = 7.1Hz), 2.67-2.75 (8H, m), 3.94 (3H, s), 4.14 (2H, t, J = 6.8 Hz), 6.70(1H, s), 6.98 (1H, d, J = 8.3 Hz), 7.20 (1H, t, J = 7.1 Hz), 7.33-7.58(9H, m). 12-35

431.5371 C (CDCl3) d 0.96(6H, t, J = 7.2 Hz), 2.57 (4H, q, J = 7.2 Hz),2.89 (2H, t, J = 5.8 Hz), 3.96 (3H, s), 4.25 (2H, t, J = 5.1 Hz), 6.98(1H, d, J =8.6 Hz), 7.16-7.60 (6H, m), 7.77 (1H, d, J = 1.9 Hz), 8.05(2H, d, J =7.6 Hz), 9.96 (1H, s). 12-36

472.5898 A (CDCl3) d 2.05 (2H, quint, J = 6.8 Hz), 2.29 (3H, s),2.31-2.58 (10H, m), 3.94 (3H, s), 4.15 (2H, t, J = 6.8 Hz), 6.74 (1H,s), 6.98 (1H, d, J =8.6 Hz), 7.20 (1H, t, J = 7.1 Hz), 7.40-7.76 (9H,m). 12-37

431.4935 A CDCl3 7.64-7.61 (m, 4H), 7.57 (dd, 1H, J = 13.8, 3.2 Hz),7.47 (s, 1H), 7.00 (s, 1H), 6.91 (d, 1H, J = 15.1 Hz), 3.92 (s, 3H),3.91 (t, 4H, J =8.2 Hz), 3.84 (s, 3H), 3.13 (t, 4H, J = 7.6 Hz) 12-38

488.5888 A CDCl3 7.67 (d, 2H, J = 9.1 Hz), 7.62 (s, 1H), 7.56 (s, 1H),7.54 (s, 2H), 7.38 (s, 1H), 6.93 (d, 2H, J = 9.1 Hz), 6.60 (d, 1H, J =8.6 Hz), 3.91 (s, 3H), 3.83 (s, 3H), 3.76 (m, 4H), 3.27 (t, 2H, J = 6.4Hz), 2.51 (m, 4H), 1.86 (t, 2H, J = 6.4 Hz) 12-39

471.6057 A CDCl3 7.77 (d, 2H, J = 7.5 Hz), 7.58 (s, 3H), 7.52 (s, 1H),7.41 (d, 2H, J = 7.9 Hz), 7.37 (s, 1H), 7.16 (t, 1H, J = 7.9 Hz), 6.62(d, 2H, J = 8.7 Hz), 3.92 (s, 3H), 3.26 (d, 2H, J = 6.2 Hz), 2.55 (m,10H), 2.32 (s, 3H), 1.85 (1, 2H, J = 6.4 Hz) 12-40

456.5472 A MeOD-d4 8.08 (s, 1H), 7.86 (d, 2H, J = 7.6 Hz), 7.68-7.26 (m,8H), 7.19 (d, 1H, J = 7.7 Hz), 3.93 (s, 3H), 3.49-3.22 (m, 6H), 2.42 (t,2H, J =8.1 Hz), 1.88 (m, 2H) 12-41

403.4835 A (CDCl3), 2.94 (3H, s), 3.34 (3H, s), 3.38 (2H, t, J = 6.0Hz), 3.58 (2H, t, J = 6.0 Hz), 3.94 (3H, s), 6.77 (1H, s), 7.00 (1H, d,J = 8.5 Hz), 7.19 (1H, t, J = 7.6 Hz), 7.43 (1H, t, J = 7.6 Hz), 7.46(1H, s), 7.52 (1H, s), 7.58 (1H, dd, J = 1.9 Hz, J = 8.2 Hz), 7.67 (1H,dd, J = 1.9 Hz, J = 8.2 Hz), 7.76 (2H, d, J = 7.6 Hz) 12-42

417.5103 A (CDCl3), 2.38 (3H, s), 2.95 (3H, s), 3.34 (3H, s), 3.39 (2H,t, J = 6.0 Hz), 3.57 (2H, t, J = 6.0 Hz), 3.96 (3H, s), 6.85 (1H, s),7.00 (1H, d, J = 8.2 Hz), 7.21 (2H, d, J = 8.2 Hz), 7.48 (2H, d, J =11.0 Hz), 7.57 (1H, dd, J = 2.2 Hz, J = 8.5 Hz), 7.64 (2H, d, J = 8.5Hz), 7.65 (2H, d, J = 1.9 Hz) 12-43

471.4806 A (CDCl3), 2.95 (3H, s), 3.35 (3H, s), 3.39 (2H, t, J = 6.0Hz), 3.59 (2H, t, J = 6.0 Hz), 3.95 (3H, s), 7.02 (2H, d, J = 8.5 Hz),7.04 (1H, s), 7.53 (1H, s), 7.56 (1H, s), 7.60 (1H, s), 7.68 (1H, d, J =3.7 Hz), 7.69 (1H, d, J = 3.5 Hz), 7.93 (2H, d, J = 8.5 Hz) 12-44

481.5743 A (CDCl3), 2.94 (3H, s), 3.06 (3H, s), 3.35 (3H, s), 3.40 (2H,t, J = 5.9 Hz), 7.03 (1H, d, J = 8.2 Hz), 7.29 (1H, t, 3.60 (2H, t, J =6.3 Hz), 3.97 (3H, s), J = 7.3 Hz), 7.58 (2H, d, J = 8.8 Hz), 7.62 (1H,s), 7.68 (1H, s), 7.74 (1H, td, J = 1.6 Hz, J = 7.3 Hz), 8.01 (1H, dd, J= 1.3 Hz, J = 7.9 Hz), 9.11 (1H, d, J = 8.2 Hz), 9.85 (1H, s) 12-45

390.4012 A (DMSO d-6) 3.82 (3H, s), 3.88 (3H, s), 7.07 (1H, s),7.70-7.79 (6H, m), 8.18 (1H, s), 8.47 (1H, s), 8.65 (1H, s), 10.04 (1H,s), 11.97 (1H, s) 12-46

482.3796 A (CDCl3), 2.95 (3H, s), 3.35 (3H, s), 3.40 (2H, t, J = 6.0Hz), 3.59 (2H, t, J = 5.9 Hz), 3.95 (3H, s), 7.01 (1H, d, J = 8.2 Hz),7.20 (1H, s), 7.50 (1H, s), 7.52 (2H, d, J = 6.9 Hz), 7.54 (1H, d, J =1.9 Hz), 7.56 (1H, s), 7.59 (1H, d, J = 1.9 Hz), 7.64 (1H, d, J = 1.0Hz), 7.71 (2H, d, J = 6.9 Hz) 12-47

415.4945 A (MeOD) 2.36 (3H, s), 3.09 (4H, t, J = 4.3 Hz), 3.84 (4H, t, J= 4.3 Hz), 3.91 (3H, s), 7.00 (1H, d, J = 8.3 Hz), 7.23 (2H, AB, J = 8.3Hz), 7.40 (1H, s), 7.55 (1H, s), 7.62 (1H, dd, J = 1.5, 8.3 Hz), 7.74(2H, AB, J = 8.3 Hz), 7.76 (1H, s), 8.05 (1H, s) 12-48

436.9009 A (CDCl3) 3.17 (4H, t, J = 4.5 Hz), 3.93 (4H, t, J = 4.5 Hz),4.00 (3H, s), 6.91 (1H, s), 7.06 (1H, d, J = 8.5 Hz), 7.23 (2H, m), 7.36(1H, dd, J = 1.9, 8.5 Hz), 7.48 (1H, d, J = 1.5 Hz), 7.66 (1H, dd, J =2.6, 8.5 Hz), 7.96 (1H, s), 8.27 (1H, d, J = 2.6 Hz) 12-49

469.4648 A (MeOD) 3.11 (4H, t, J = 4.5 Hz), 3.85 (4H, t, J = 4.5 Hz),3.93 (3H, s), 7.03 (1H, d, J = 8.3 Hz), 7.49 (1H, s), 7.60 (1H, d, J =1.5 Hz), 7.65 (1H, dd, J = 1.9, 8.3 Hz), 7.69 (1H, s), 7.73 (2H, AB, J =4.5 Hz), 8.10 (3H, m) 12-50

372.4906 A CDCl3 7.65 (s, 1H), 7.63 (s, 2H), 7.63 (s, 2H), 7.47 (s, 1H),7.26 (m, 1H), 7.02 (d, 1H, J = 8.9 Hz), 3.96 (s, 3H), 3.59 (t, 1H, J =6.0 Hz), 3.51 (q, 2H, J = 7.3 Hz), 3.40 (t, 2H, J = 6.2 Hz), 3.35 (s,3H), 2.95 (s, 1.59 (t, 3H, J = 7.3 Hz) 12-51

433.5093 A CDCl3 7.64 (d, 2H, J = 9.3 Hz), 7.62 (s, 2H), 7.63 (s, 1H),7.59 (s, 1H), 7.52 (s, 1H), 7.43 (s, 1H), 6.97 (d, 1H, J = 8.2 Hz), 6.94(d, 2H, J = 9.3 Hz), 3.90 (s, 3H), 3.83 (s, 3H), 3.57 (1, 2H, J = 6.0Hz), 3.36 (q, 2H, J = 6.0 Hz), 3.34 (s, 3H), 2.92 (s, 3H) 12-52

389.4567 A CDCl3 7.72 (s, 1H), 7.68 (d, 2H, J =8.8 Hz), 7.63 (s, 1H),7.58 (s, 1H), 7.54 (d, 1H, J = 8.5 Hz), 7.43 (s, 1H), 6.96 (d, 1H, J =8.5 Hz), 6.93 (d, 2H, J = 8.9 Hz), 3.98 (s, 3H), 3.83 (s, 3H), 2.89 (s,6H) 12-53

480.3638 A CDCl3 7.94 (br s, 1H), 7.77 (s, 2H), 7.74 (s, 1H), 7.62 (s,2H), 7.59 (d, 1H, J = 13.8 Hz), 7.52 s), 7.48 (s, 2H), 6.97 (d, 1H, J =13.8 Hz), 3.95 (s, 3H), 3.91 (t, 4H, J = 7.6 Hz), 3.14 (t, 4H, J = 7.6Hz) 12-54

401.4677 A CDCl3 7.80 (d, 2H, J = 7.9 Hz), 7.69 (s, 1H), 7.67 (s, 1H),7.63 (s, 1H), 7.59 (dd, 1H, J = 8.2, 1.9 Hz), 7.50 s), 7.40 (t, 2H, J =8.1 Hz), 7.18 (t, 1H, J = 7.4 Hz), 6.97 (d, 1H, J = 8.2 Hz), 3.94 (s,3H), 3.91 (t, 4H, J =4.6 Hz), 3.14 (t, 4H, J = 4.5 Hz) 12-55

502.6156 A CDCl3 7.74-7.52 (m, 6H), 7.44 (s, 1H), 7.20 (brs, 1H), 6.93(d, 3H, J =15.0 Hz), 3.90 (s, 3H), 3.83 (s, 3H), 3.70 (t, 4H, J = 7.7Hz), 3.18 (t, 2H, J = 12.6 Hz), 2.83 (s, 3H), 2.43-2.33 (m, 6H) 12-56

447.5361 A CDCl3 7.65 (d, 2H, J = 8.9 Hz), 7.61 (s, 1H), 7.58 (d, 1H, J= 6.0 Hz), 7.52 (d, 1H, J = 8.2 Hz), 7.43 (s, 1H), 6.98-6.92 (m, 3H),3.95 (m, 4H), 3.83 (s, 3H), 3.41 (t, 2H, J =6.3 Hz), 3.31 (s, 3H), 3.22(t, 2H, J = 7.6 Hz), 2.84 (s, 3H), 1.84 (m, 2H) 12-57

479.562 A CDCl3 9.87 (s, 1H), 9.10 (d, 1H, J = 8.5 Hz), 8.01 (d, 1H, J =7.9 Hz), 7.26 (t, 1H, J =8.5 Hz), 7.69 (s, 1H), 7.64-7.59 (m, 4H), 7.30(t, 1H, J =6.9 Hz), 7.02 (d, 1H, J = 7.9 Hz), 3.99 (s, 3H), 3.92 (t, 4H,J = 4.1 Hz), 3.17 (s, 7H) 12-58

417.4715 418 DMSO 10.44 (s, 1H), 8.74 (d, 1H, J = 2.2 Hz), 8.09 (d, 1H,J = 2.2 Hz), 7.70 (m, 2H, ), 7.69 (s, 1H), 7.64-7.59 (m, 3H), 7.010 (d,1H, J = 8.9 Hz), 6.88 (d, 1H, J = 8.8 Hz), 3.87 (s, 3H), 3.75 (f, 4H, J= 4.1 Hz), 3.09 (t, 4H, J = 4.2 Hz) 12-59

441.4927 A 442 (MeOD) 3.14 (4H, t, J = 4.4 Hz), 3.87 (4H, t, J = 4.4Hz), 4.01 (3H, s), 6.85 (1H, dd, J = 1.9, 8.5 Hz), 7.10 (1H, d, J = 8.5Hz), 761 (1H, d, J = 8.5 Hz), 7.65 (1H, d, J = 1.3 Hz), 7.78 (1H, dd, J= 1.9, 8.5 Hz), 7.80 (1H, s), 7.85 (1H, s), 7.88 (1H, d, J = 1.9 Hz),8.22 (1H, s), 8.91 (1H, s) 12-60

479.5585 A 480 (MeOD) 3.09 (4H, t, J = 4.7 Hz), 3.16 (3H, s), 3.85 (4H,t, J = 4.7 Hz), 3.94 (3H, s), 7.02 (1H, d, J = 8.5 Hz), 7.49 (1H, d, J =0.6 Hz), 7.60 (1H, d, J = 1.6 Hz), 7.67 (2H, m), 7.72 (2H, m), 8.12 (1H,d, J = 0.6 Hz), 8.16 (1H, m), 8.72 (1H, t, J = 1.9 Hz) 12-61

390.4049 B 391

Example 13

[0288]

[0289] A solution of5-chloro-7-(3,4-dimethoxyphenyl)-imidazo[1,2-c]pyrimidine 0.26 mmol andthiophenol 0.52 mmol in DMSO was stirred overnight at room temperature.The reaction mixture was neutralized with sat. NaHCO₃ solution anddiluted with water and extracted with CHCl₃. The organic extracts werewashed with brine, and dried over Na₂SO₄. The resulting product,5-phenylsulfenyl-7-(3,4-dimethoxyphenyl)imidazo[1,2-c]pyrimidine, wasconcentrated and purified by column chromatography.

[0290] Molecular weight 363.4414

[0291] Mass spectrometry: 364

[0292] Activity grade: A

[0293] With the use of any of the intermediates I or II and according tothe procedure that is similar to that of Example 13, following compoundsshown in Table 12 below were prepared. TABLE 12 Activity Ex. No.MOLSTRUCTURE MOLWEIGHT grade MS NMR 13-1

391.4956 B 13-2

393.4679 A 13-3

378.4561 A 13-4

378.4561 A 13-5

432.3315 C 13-6

442.3374 A 13-7

393.4679 A 13-8

453.5209 A 454 (DMSO-d6) 3.63 (s, 3H), 3.76 (s, 3H), 3.77 (s, 3H), 3.80(s, 3H), 6.95 (d, 1H, J = 8.53 Hz), 7.14 (s, 2H), 7.41 (d, 2H, J = 1.99Hz), 7.57 (dd, 1H), 7.75 (d, 1H, J = 1.40 Hz), 7.97 (d, 2H, J = 8.02Hz). 13-9

391.4956 C (CDCl3) 2.48 (s, 6H), 3.65 (s, 3H), 3.88 (s, 3H), 6.84 (d,1H, J = 8.464 Hz), 7.21-7.37 (m, 5H), 7.65-7.71 (m, 3H). 13-10

432.3315 B (CDCl3) 3.73 (s, 3H), 3.89 (s, 3H), 6.85 (d, 1H, J = 8.45Hz), 7.24 (d, 1H, J = 2.09 Hz), 7.32-7.35 (m, 1H), 7.38-7.44 (m, 1H),7.54-7.57 (m, 2H), 7.65-7.67 (m, 2H), 7.72 (d, 1H, J = 1.43 Hz). 13-11

420.5153 A 421 (CDCl3) 3.60 (3H, s), 3.92 (3H, s), 6.92 (1H, d, J = 8.2Hz), 7.45-7.58 (4H, m), 7.64 (1H, s), 7.76 (2H, d, J = 12.6 Hz), 7.89(1H, d, J = 7.3 hz), 8.12 (2H, d, J = 7.3 Hz). 13-12

367.4325 A 368 (CDCl3) 3.78 (3H, s), 3.85 (3H, s), 3.91 (3H, s), 6.88(1H, d, J = 8.5 Hz), 7.25 (1H, s), 7.35 (1H, d, J = 8.5 Hz), 7.61 (1H,s), 7.68 (1H, s), 7.71 (1H, s). 13-13

365.4166 A 366 (CDCl3) 3.94 (3H, s), 3.98 (3H, s), 6.97 (1H, d, J = 8.9Hz), 7.10 (1H, t, J = 4.9 Hz), 7.58 (1H, s), 7.62-7.66 (2H, m), 7.96(1H, s), 8.50 (1H, d, J = 4.9 Hz). 13-14

418.5214 A 419 (DMSO) 2.58 (1H, bs), 2.75 (2H, t, J = 5.3 Hz), 2.98 (2H,t, J = 5.3 Hz), 3.61 (3H, s), 3.78 (3H, s), 3.89 (2H, s), 6.95 (1H, d, J= 8.5 Hz), 7.29 (1H, d, J = 7.9 Hz), 7.34 (1H, s), 7.45 (1H, s), 7.51(1H, d, J = 7.9 Hz), 7.56 (1H, d, J = 8.5 Hz), 7.96 (2H, d, J = 6.3 Hz).13-15

363.4414 364 (DMSO-d6) 3.78 (3H, s), 3.87 (3H, s), 7.16 (1H, d, J = 8.4Hz), 7.32-7.40 (5H, m), 7.75 (1H, d, J = 1.4 Hz), 7.89-7.92 (2H, m),7.99-8.03 (2H, m) 13-16

461.5902 A (CDCl3) 2.37 (3H, s), 2.58 (4H, t, J =5.1 Hz), 3.31 (4H, t, J= 5.0 Hz), 3.70 (3H, s), 3.89 (3H, s), 6.85 (1H, d, J = 8.5 Hz), 6.98(2H, d, J = 8.9 Hz), 7.35-7.42 (2H, m), 7.55-7.67 (5H, m) 13-17

303.3884 304 (DMSO-d6) 7.35-7.37 (3H, m), 7.59-7.65 (3H, m), 7.79-7.85(5H, m), 8.06 (2H, s) 13-18

333.4149 334 (DMSO-d6) 3.77 (3H, s), 6.89 (2H, d, J = 8.9 Hz), 7.58-7.64(3H, m), 7.74-7.80 (5H, m), 7.95 (2H, d, J =12.3) 13-19

421.4751 C-D (DMSO-d6) d 3.51 (3H, s), 3.54 (2H, s), 3.73 (3H, s), 6.82(1H, s), 6.89 (2H, s), 7.12-7.23 (4H, m), 7.55 (1H, d, J = 1 Hz), 8.19(1H, d, J = 1 Hz), 12.28 (1H, s) 13-20

421.4784 A 422 13-21

449.5287 C (DMSO-d6) d 1.72-1.86 (2H, m), 2.14-2.27 (2H, m), 2.56-2.62(2H, m), 3.53 (3H, s), 3.73 (3H, s), 6.82-6.90 (3H, m), 7.11 (2H, d, J =8 Hz), 7.18 (2H, d, J = 8 Hz), 7.55 (1H, s), 8.19 (1H, s), 12.01 (1H,s), 13.43 (1H, s) 13-22

447.5167 A 448 13-23

475.5709 B 476 (CDCl3) 1.83 (1H, m), 2.22-2.27 (1H, m), 2.70-2.99 (3H,m), 3.07 (2H, d, J = 7.7 Hz), 3.74 (3H, s), 3.75 (3H, s), 3.90 (3H, s),6.87 (1H, d, J = 8.4 Hz), 7.34 (1H, s, J = 2.0 Hz), 7.36-7.51 (3H, m),7.60 (1H, s), 7.67 (1H, s), 7.68 (1H, s). 13-24

421.4751 A 422 (DMSO d-6) d 2.64 (2H, t, J = 7.5 Hz), 2.96 (2H, t, J =7.5 Hz), 3.80 (3H, s), 6.91 (1H, d, J = 8.5 Hz), 7.24 (1H, dd, J = 2.2,8.5 Hz), 7.29 (1H, d, J = 2.2 Hz), 7.47 (2H, d, J =8.2 Hz), 7.67 (1H, d,J = 8.2 Hz), 7.83 (1H, s), 7.89 (1H, d, J = 1.6 Hz), 13-25

463.5119 A 464 (CDCl3) d 2.36 (3H, s), 2.82 (2H, t, J = 7.0 Hz), 3.10(2H, t, J = 7.0 Hz), 3.80 (3H, s), 6.72 (1H, d, J = 8.6 Hz), 722-7.28(3H, m), 7.45 (3H, m), 7.62 (3H, m). 13-26

511.5995 A 512 (CDCl3) d 2.76 (2H, t, J = 7.5 Hz), 3.06 (2H, t, J = 7.5Hz), 3.78 (3H, s), 5.16 (2H, s), 6.83 (1H, d, J = 8.5 Hz), 6.90-7.45(9H, m), 7.53 (2H, d, J = 2.0 Hz), 7.64-7.68 (3H, m). 13-27

421.4751 A 422 (CDCl3) d 2.77 (2H, t, J = 7.5 Hz), 3.06 (2H, t, J = 7.5Hz), 3.78 (3H, s), 6.86 (1H, d, J = 8.0 Hz), 7.15-7.32 (3H, m), 7.39(2H, d, J = 8.2 Hz), 7.53 (2H, d), 7.68 (3H, m). 13-28

534.634 A (DMSO d-6) d 2.62 (2H, t, J = 7.5 Hz), 2.92 (2H, t, J = 7.5Hz), 3.15-3.55 (6H, m), 3.68 (3H, s), 3.77 (2H, broad 1), 3.97 (2H,broad t), 4.41 (2H, t, J = 4.7 Hz), 7.06 (1H, d, J = 8.5 Hz), 7.41 (1H,d, J = 1.9 Hz), 7.47 (2H, d, J = 8.2 Hz), 7.54 (1H, dd, 13-29

354.393 A (DMSO) 3.74 (3H, s), 3.79 (3H, s), 6.97 (1H, d, J = 8.5 Hz),7.06 (1H, d, J = 8.2 Hz), 7.36 (1H, d, J = 1.9 Hz), 7.40 (1H, s),7.41-7.44 (1H, m), 7.51 (1H, d, J = 1.9 Hz), 7.80 (1H, s), 8.06 (1H, s).

Example 14

[0294]

[0295] To a suspension of5-Chloro-7-(3-methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidine(2.0 g, 5.80 mmol) in DMF was added NaH (60% in mineral oil, 197 mg,4.93 mmol) at 0° C. under an Ar atmosphere. After 10 min,2-aminonicitinic methyl ester (1.06 g, 6.96 mmol) was added, followed byanother portion of NaH (60% in mineral oil, 197 mg, 4.93 mmol). Then thereaction mixture was stirred at room temperature overnight. Afterquenching with 0.3 ml of acetic acid, the reaction mixture was pouredinto water. The organic layer was extracted with CH₂Cl₂ and the combinedorganic layer was dried over MgSO₄. After concentration in vacuo, themixture containing2-[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinicacid methyl ester was used for the next step without furtherpurification.

[0296] The mixture of the above methyl ester in saturated ammonia inEtOH (20 mL) was stirred for 3 days. The incoming solid was collected byfiltration and eluted with MeOH. Vacuum oven dry gave2-[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamideas a pale yellow solid (780 mg, 40%).

[0297] Activity grade:A

[0298] With the use of any of the intermediates I or II and according tothe procedure that is similar to that of Example 14, following compoundsshown in Table 13 below were prepared. TABLE 13 Ex. No. MOLSTRUCTUREMOLWEIGHT Activity grade MS NMR 14-1

407.495 B (DMSO) 3.72 (3H, s), 3.83 (3H, s), 3.86 (3H, s), 4.80 (2H, s),6.89 (2H, d, 8.6 Hz), 7.09 (1H, d, J = 8.4 Hz), 7.47 (2H, d, J = 8.6Hz), 7.69 (1H, s), 7.81 (1H, s), 7.84 (1H, dd, J = 2.0 Hz, 8.4 Hz), 8.01(1H, s). 14-2

377.4685 A (DMSO) 3.83 (3H, s), 3.84 (3H, s), 4.85 (2H, s), 7.08 (1H, d,J = 8.5 Hz), 7.28-7.37 (3H, m), 7.56 (2H, d, J = 8.4 Hz), 7.71 (1H, s),7.78 (1H, s), 7.78-7.86 (2H, m), 8.01 (1H, s). 14-3

361.4039 B 14-4

426.2728 B 14-5

426.2728 B 14-6

426.2728 B 14-7

304.376 C 305 (CDCl3) 7.30-7.40 (3H, m), 7.70-7.60 (4H, m), 7.65-7.81(5h, m), 8.43 (1H, s) 14-8

320.3754 C 321 (DMSO d-6) 6.98 (2H, d, J = 8.6 Hz), 7.36-7.43 (3H, m),7.58 (2H, d, J = 8.6 Hz), 7.90-7.93 (2H, m), 8.23 (1h, s), 8.70 (1H, s)14-9

339.8086 C-D 340 14-10

434.4771 A 435 (DMSO d-6) 3.53 (3H, s), 3.78 (3H, s), 6.6.70 (1H, d, J =16.0 Hz), 6.97 (1H, d, J = 8.6 Hz), 7.31 (1H, d, J =2.0 Hz), 7.60-7.95(6H, m), 8.32 (1H, s), 8.68 (1H, s), 12.53 (1H, br) 14-11

437.4807 A 438 (CDCl3) 3.63 (3H, s), 3.79 (3H, s), 3.89 (2H, s), 6.74(2H, d, J = 8.7 Hz), 6.98 (1H, d, J = 8.5 Hz), 8.16 (1H, s), 8.64 (1H,s), 12.66 (1H, br) 14-12

420.4285 B 421 (DMSO d-6) 2.59 (2H, t, J = 7.5 Hz), 2.91 (2H, t, J = 7.5Hz), 3.83 (3H, s), 3.88 (3H, s), 7.00 (1H, d, J =8.5 Hz), 7.09 (1H, d, J= 8.3 Hz), 7.14 (1H, s), 7.47-7.59 (m), 8.40 (1H, s), 8.63 (1H, s),12.13 (1H, br) 14-13

445.4669 C 446 (DMSO) 3.82 (3H, s), 3.83, (3H, s), 4.94 (2H, s), 7.06(1H, d, J = 8.5 Hz), 7.54-7.65 (2H, m), 7.70 (1H, s), 7.75 (1H, d, J =2.1 Hz), 7.81 (1H, dd, J = 2.1 Hz, 8.5 Hz), 7.85 (2H, m), 7.96 (1H, s),8.01 (1H, s). 14-14

387.4609 B 388 (DMSO) 1.06 (3H, t, d = 7.1 Hz), 1.75 (3H, d, J = 7.3Hz), 3.83 (3H, s), 3.91 (3H, s), 4.05-4.15 (2H, m), 4.84 (1H, q, J = 7.3Hz), 7.06 (1H, d, J = 8.2 Hz), 7.71 (1H, d, J = 1.5 Hz), 7.76-7.79 (2H,m), 7.86 (1H, s), 8.02 (1H, s). 14-15

411.9135 B 412 (DMSO) 3.83 (3H, s), 3.84 (3H, s), 4.85 (2H, s), 7.41(2H, d, J = 8.4 Hz), 7.58 (2H, d, J = 8.4 Hz), 7.75 (2H, s), 7.81-7.88(2H, m), 8.03 (1H, s). 14-16

369.3681 A 370 (DMSO) 3.83 (3H, s), 3.88 (3H, s), 4.67 (2H, q, J = 10.2Hz), 7.09 (1H, d, J = 8.2 Hz), 7.76-7.82 (3H, m), 7.98 (1H, s), 8.08(1H, s). 14-17

329.4239 A 330 (DMSO) 1.08 (3H, t, J = 7.3 Hz), 1.91 (2H, h, J = 7.3Hz), 3.50 (2H, t, J = 7.3 Hz), 3.83 (3H, s), 3.88 (3H, s), 7.09 (1H, d,8.3 Hz), 7.69 (1H, d, J = 1.4 Hz), 7.78-7.81 (3H, m), 7.99 (1H, s).14-18

371.5052 C-D 372 (DMSO) 0.86 (3H, t, J = 6.9 Hz), 1.25-1.35 (4H, m),1.44-1.52 (2H, m), 1.86 (2H, p, J = 7.3 Hz), 3.52 (2H, t, J = 7.3 Hz),3.83 (3H, s), 3.88 (3H, s), 7.07 (1H, d, J = 8.3 Hz), 7.69 (1H, d, J =1.5 Hz), 7.77-7.82 (3H, m), 7.98 (1H, s). 14-19

414.574 B 415 (DMSO) 0.98 (12H, d, J = 6.6 Hz), 2.87 (2H, t, J = 7.1Hz), 3.04-3.08 (2H, m), 3.57 (2H, t, J = 7.1 Hz), 3.82 (3H, s), 3.88(3H, s), 7.06 (1H, d, J = 8.5 Hz), 7.68 (1H, s), 7.74 (1H, s), 7.78-7.82(2H, m), 7.96 (1H, s). 14-20

343.451 A 344 (DMSO) 1.08 (3H, t, J = 7.4 Hz), 1.57 (3H, d, J = 6.9 Hz),1.86-1.95 (2H, m), 3.83 (3H, s), 3.88 (3H, s), 4.22-4.25 (1H, m), 4.23(1H, d, J = 8.4 Hz), 7.68 (1H, d, J = 1.5 Hz), 7.76-7.81 (3H, m), 7.99(1H, s). 14-21

355.4621 A 356 (DMSO) 1.72-1.82 (6H, ), 2.34-2.42 (2H, m), 3.83 (3H, s),3.88 (3H, s), 4.37-4.42 (1H, m), 7.09 (1H, d, J = 9.0 Hz), 7.68 (1H, d,J = 1.4 Hz), 7.77-7.82 (3H, m), 7.98 (1H, s). 14-22

343.451 A 344 (DMSO) 1.09 (6H, d, J = 6.7 Hz), 2.12-2.20 (1H, m), 3.46(2H, d, J = 6.7 Hz), 3.83 (3H, s), 3.89 (3H, s), 7.09 (1H, d, J = 8.4Hz), 7.70 (1H, d, J = 1.5 Hz), 7.77-7.82 (2H, m), 7.84 (1H, s), 7.99(1H, s). 14-23

357.4781 B 358 (DMSO) 0.93 (3H, t, J = 7.4 Hz), 1.06 (3H, d, J = 6.7Hz), 3.42 (1H, dd, J = 7.3 Hz, 13.2 Hz), 3.59 (1H, dd, (3H, s), 7.08(1H, d, J = 8.3 Hz), 7.69 (1H, s), 7.77-7.84 (3H, m), 7.98 (1H, s).14-24

430.5298 B 431 (DMSO) 1.36 (9H, s), 3.47 (2H, bq), 3.59(2H, bt), 3.82(3H, s), 3.89 (3H, s), 7.06 (1H, d, J = 8.5 Hz), 7.14 (1H, bt), 7.69(1H, d, J = 1.4 Hz), 7.76-7.85 (3H, m), 7.99 (1H, s). 14-25

391.4956 B 392 (DMSO) 3.17 (2H, t, J = 7.9 Hz), 3.15-3.20 (8H, m), 7.08(1H, d, J = 8.5 Hz), 7.20-7.36 (5H, m), 7.69 (1H, s), 7.78 (1H, d, J =2.0 Hz), 7.82 (1H, s), 7.84 (1H, d, J = 2.0 Hz), 7.99 (1H, s). 14-26

357.4781 B 358 (DMSO) 0.88 (3H, t, J = 7.2 Hz), 1.25-1.50 (4H, m), 1.87(2H, p, J = 7.3 Hz), 3.52 (2H, t, J = 7.2 Hz), 3.83 (3H, s), 3.88 (3H,s), 7.08 (1H, d, J = 8.3 Hz), 7.69(1H, s), 7.77-7.82 (3H, m), 7.98 (1H,s). 14-27

358.4657 A 359 (DMSO) 2.75 (2H, t, J = 6.8 Hz), 3.68 (2H, t, J = 6.8Hz), 3.82 (3H, s), 3.88 (3H, s), 7.07 (1H, d, J = 8.5 Hz), 7.69 (1H, s),7.77-7.84 (3H, m), 7.98 (1H, s). 14-28

357.4781 B 358 (DMSO) 0.97 (6H, d, J = 6.2 Hz), 1.73-1.80 (3H, m), 3.54(2H, t, J = 7.4 Hz), 3.83 (3H, s), 3.88 (3H, s), 7.07 (1H, d, J = 8.4Hz), 7.69 (1H, d, J = 1.4 Hz), 7.76-7.83 (3H, m), 7.98 (1H, s). 14-29

369.4892 A 370 (DMSO) 1.47-1.98 (8H, m), 2.23-2.28 (2H, m), 3.83 (3H,s), 3.89 (3H, s), 4.21-4.25 (1H, m), 7.09 (1H, d, J = 9.0 Hz), 7.68 (1H,d, J = 1.5 Hz), 7.77-7.80 (3H, m), 7.98 (1H, s). 14-30

395.459 B 396 (DMSO) 3.83 (3H, s), 3.85 (3H, s), 4.85 (2H, s), 7.08 (1H,d, J = 8.5 Hz), 7.14-7.20 (2H, m), 7.57-7.62 (2H, m), 7.69 (1H, s), 7.77(1H, s), 7.85 (2H, d, J = 8.5), 8.02 (1H, s). 14-31

383.4943 A 384 (DMSO) 3.83 (3H, s), 3.86 (3H, s), 6.93-6.96 (1H, m),7.08 (1H, d, J = 8.5 Hz), 7.21 (1H, d, J = 3.4 Hz), 7.38 (1H, d, J = 5.2Hz), 7.70 (1H, s), 7.82-7.90 (3H, m), 8.04 (1H, s). 14-32

393.4708 A 394 (DMSO) 3.44 (2H, t, J = 7.1 Hz), 3.83 (6H, s), 3.96 (2H,t, J = 7.1 Hz), 7.05 (1H, d, J = 8.5 Hz), 7.68 (1H, s), 7.80 (2H, s),7.85 (1H, dd, J = 2.1 Hz, 8.5 Hz), 7.99 (1H, s), 8.51 (1H, d, J = 2.5Hz), 8.59-8.61 (1H, m), 8.64 (1H, d, J = 1.4 Hz). 14-33

358.422 A 359 (DMSO) 2.63 (3H, d, J = 4.6 Hz), 3.82 (3H, s), 3.89 (3H,s), 4.23 (2H, s), 7.04 (1H, d, J = 8.4 Hz), 7.71 (1H, s), 7.47 (1H, d, J= 2.1 Hz), 7.79 (1H, dd, J = 2.1 Hz, 8.4 Hz), 7.89 (1H, s), 7.98 (1H,s), 8.23(1H, bq). 14-34

478.5268 A 479 14-35

434.4102 B (CDCl3), 3.94 (3H, s), 3.97 (3H, s), 6.85 (1H, d, J = 2.8Hz), 6.99 (2H, d, J = 4.7 Hz), 7.49 (1H, s), 7.65 (2H, s), 7.67 (2H, d,J = 4.8 Hz), 7.84 (2H, d, J = 2.8 Hz), 7.99 (1H, s), 8.02 (1H, s) 14-36

405.4167 C 406

Exampl 15

[0299]

[0300] A suspension of5-Chloro-7-(3,4-dimethoxy-phenyl)-imidazo[1,2-c]pyrimidine (50 mg, 0.17mmol), 2-Mercapto-benzoicacid (53 mg, 0.35 mmol) and K₂CO₃ (48 mg, 0.35mmol) in EtOH was stirred at room temperature overnight. Water was addedto the reaction mixture. Extraction was carried out with CHCl₃ afterneutralization with 1N HCl. The CHCl₃ layer was washed with water andthen dried over Na₂SO₄. The organic layer was then concentrated to givethe crude product. The resulting2-(7-Phenyl-imidazo[1,2-c]pyrimidin-5-ylsulfanyl)-benzoic acid waspurified by recrystalization from MeOH (40 mg, 57%).

[0301] With the use of any of the intermediates I or II and according tothe procedure that is similar to that of Example 15, following compoundsshown in Table 14 below were prepared. TABLE 14 Ex. No. MOLSTRUCTUREMOLWEIGH Activity grade MS NMR 15-1

432.4274 A 433 15-2

408.4389 A 409 15-3

453.5424 A 454 15-4

352.4399 B 353 (CD3OD) 0.85-2.30 (11H, m), 3.88 (3H, s), 3.92 (3H, s),7.03 (1H, d, J = 8.4), 7.21 (1H, s), 7.45 (1H, d, J = 1.5), 7.65-7.75(1H, m), 7.77 (1H, s), 7.84 (1H, s)

Example 16

[0302]

[0303] 7-(3,4-Dimethoxy-phenyl)-5-ethylsulfanyl-imidazo[1,2-c]pyrimidine(335 mg, 1.06 mmol) was dissolved in trifluoroacetic acid (TFA, 5 ml).After 5 min the TFA was evaporated. The residue was dissolved in 10 mlCH₂Cl₂. The solution was cooled to 0° C. and m-CPBA (70%, 524 mg, 2.12mmol) was added. The reaction mixture was allowed to warm to roomtemperature and was stirred for 5 h. Diisopropylamine (598 mg, 4.63mmol) and thiol (254 mg, 2.28 mmol) were added and the mixture wasstirred at room temperature overnight. Water was added to the reactionmixture and extraction was carried out with CHCl₃. The organic layer waswashed with brine, sat. NaHCO₃, brine and dried over Na₂SO₄. The organiclayer was then concentrated to give the crude product of7-(3,4-Dimethoxy-phenyl)-5-(pyridin-4-ylsulfanyl)-imidazo[1,2-c]pyrimidinewhich was purified by column chromatography (160 mg, 41%).

[0304] Molecular weight: 364.429

[0305] Mass spectrometry: 365

[0306] Activity grade:A

[0307]¹H-NMR: (DMSO-d6) 3.67 (s, 3H), 3.78 (s, 3H), 6.97 (d, 1H, J=8.52Hz), 7.38 (d, 1H, J=2.06 Hz), 7.54 (dd, 1H), 7.76 (d, 1H, J=1.45 Hz),7.80-7.83 (m, 2H) , 8.00 (s, 1H), 8.09 (s, 1H), 8.74-8.76 (m, 2H).

[0308] With the use of any of the intermediates I or II and according tothe procedure that is similar to that of Example 16, following compoundsshown in Table 15 below were prepared. TABLE 15 Ex. No. MOLSTRUCTUREMOLWEIGHT Activity grade MS NMR 16-1

369.4077 A (DMSO-d6) 3.75 (s, 3H), 3.79 (s, 3H), 4.16 (s, 3H), 6.98 (d,1H, J =9.00 Hz), 7.15 (d, 1H, J = 2.00 Hz), 7.38 (dd, 1H), 7.81 (d, 1H,J = 1.45 Hz), 8.18 (s, 1H), 8.18 (d, 1H, J =0.69 Hz) 16-2

510.6383 A (DMSO-d6) 1.38-1.44 (m, 2H), 1.56-1.65 (m, 4H), 2.95-2.98 (m,4H), 3.66 (s, 3H), 3.76 (s, 3H), 6.89 (d, 1H, J = 8.55 Hz), 7.36 (d, 1H,J =1.98 Hz), 7.48 (dd, 1H), 7.77 (d, 1H, J = 1.47 Hz), 7.91 (d, 2H, J=8.42 Hz), 8.02-8.09 (m, 4H) 16-3

387.3862 388 (DMSO-d6) 7.34 (2H, d, J = 8.2 Hz), 7.57-7.64 (3H, m),7.78-7.81 (3H, m), 7.94-7.97 (2H, m), 8.04 (1H, s), 8.12 (1H, s) 16-4

402.4008 403 5(DMSO-d6) 5.70 (2H, s), 6.73 (2H, d, J = 8.5 Hz),7.33-7.38 (4H, m), 7.77 (1H, s), 7.97-8.06 (4H, m) 16-5

496.6113 A 497 (DMSO-d6) (m m 3.65 (s, 3H), 3.77 (s, 3H), 6.90 (d, 1H, J= 8.52 Hz), 7.35 (d, 1H, J = 1.88 Hz), 7.49 (dd, 1H,), 7.77 (d, 1H, J =1.29 Hz), 7.97-8.08 (m, 6H). 16-6

512.6107 ND 513 (DMSO-d6) .95- 3.00 (m, 6570 (m 3.69 (s, 3H), 3.75 (s,3H), 6.92 (d, 1H, J = 8.56 Hz), 7.36 (dd, 1H,), 7.42 (d, 1H, J = 1.95Hz), 7.77 (d, 1H, J = 1.38 Hz), 7.93 (d, 2H, J = 8.45 Hz), 8.03-8.11 (m,4H). 16-7

379.4437 A 380 (DMSO) 3.64 (s, 3H), 3.77 (s, 3H), 5.94 (br, 2H), 6.94(d, 1H, J = 8.51 Hz), 7.38-7.40 (m, 2H), 7.52 (dd, 1H), 7.73 (d, 1H, J =1.42 Hz), 7.82 (d, 1H, J = 4.94 Hz), 7.96 (d, 2H, J =2.18 Hz), 8.24 (s,1H).

Example 17

[0309]

[0310] To a solution of4-(5-ethylsulfanyl-imidazo[1,2-c]pyrimidin-7-yl)-2-methoxy-phenol (7.5g, 18.1 mmol) in 15 ml of THF was added NaH (2.3 g, 56.6 mmol) at 0° C.After 15 min. at 0° C., N-phenyltrifluromethane sulfonamide (10.2 g,28.6 mmol) was added. The reaction mixture was stirred at 0° C. for 1 hand then warmed to room temperature. After 1 h, the reaction mixture wasconcentrated in vacuo. The residue was purified by column chromatographyto give the triflate as a light yellow solid (6.3 g, 80%).

[0311] A mixture of the starting triflate (100 mg, 0.23 mmol),di-t-butyl-2-biphenylphosphine (17 mg, 0.06 mmol), Pd₂(dba)₃ (21 mg,0.02 mmol) and cesium carbonate (113 mg, 0.35 mmol) in a sealed tube wasdegassed with vigorous stirring and filled with Ar atmosphere. Afterdioxane (5 ml) and the corresponding amine (50 mg, 1.62 mmol) wereadded, the mixture was heated at 130-135° C. for 1 d. Cooled to roomtemperature, the mixture was diluted with 30 ml of CHCl₃ and filteredthrough a Celite pad. The filtrate was concentrated and the residue waspurified by preparative thin layer chromatography to give[4-(5-Ethylsulfanyl-imidazo[1,2-c]pyrimidin-7-yl)-2-methoxy-phenyl]-methyl-amine(49 mg, 68%).

[0312] To a solution of the secondary amine (45 mg, 0.14 mmol),formaldehyde (37% in aqueous solution, 30 mg, 1.00 mmol) and NaBH₃CN (15mg, 0.24 mmol) in 5 ml of MeOH was added 0.8 ml of 1N HCl. Afterstirring at room temperature overnight, the reaction was quenched with0.5 ml of 1N NaOH. After evaporation, the residue was purified bypreparative thin layer chromatography to give tertiary amine (31 mg,66%).

[0313] With the use of any of the intermediates I or II and according tothe procedure that is similar to that of Example 17, following compoundsshown in Table 16 below were prepared. TABLE 16 Ex. Activity No.MOLSTRUCTURE MOLWEIGHT grade MS NMR 17-1

399.5601 B CDCl3 7.62 (s, 2H), 7.45 (s, 1H), 7.44 (dd, 1H, J = 8.7, 2.3Hz), 7.30 (d, 1H, J = 2.3 Hz), 6.86 (d, 1H, J =8.3 Hz), 3.91 (s, 3H),3.50 (q, 2H J = 7.4 Hz), 3.29 (t, 2H, J = 6.4 Hz), 2.80 (t, 1H, J = 7.3Hz), 2.62 (s, 6H), 1.82 (m, 4K), 1.57 (t, 3H, J =7.3 Hz) 17-2

314.4112 B CDCl3 7.66 (s, 1H), 7.62 (s, 1H), 7.46 (s, 1H), 7.43 (dd, 1H,J = 8.3, 2.3 Hz), 7.34 (d, 1H, J = 2.3 Hz), 6.85 (d, 1H, J = 8.3 Hz),3.91 (s, 3H), 3.51 (q, 2H, J = 7.3 Hz), 2.96 (s, 3H), 1.5 (t, 3H, J =7.4 Hz) 17-3

425.5543 A CDCl3 7.71-7.52 (m, 3H), 7.43 (s, 1H), 7.36 (dd, 1H, J =3.8Hz), 6.65 (d, 1H, J = 8.3 Hz), 3.93 (s, 3H), 3.51 (q, 2H, J = 7.4 Hz),3.41 (m, 4H), 3.25 (t, 2H, J = 6.8 HZ), 2.41 (t, 2H, J = 8.1 HZ), 2.03(p, 2H, J = 7.7 HZ), 1.88 (p, 2H, J = 7.3 HZ), 1.60 (t, 3H, J =7.4 HZ)17-4

440.6128 A CDCl3 7.67 (d, 1H, J = 8.3 Hz), 7.56 (s, 2H), 7.45 (s, 1H),7.23 (m, 1H), 6.67 (d, 1H, J = 8.3 Hz), 3.97 (s, 3H), 3.52 (q, 2H, J =7.3 Hz), 3.27 (t, 2H, J = 6.4 Hz), 2.54 (m, 8H), 2.35 (s, 3H), 1.88 (m,2H), 1.59 (t, 3H, J = 7.4 Hz) 17-5

399.5601 B CDCl3 7.75 (d, 1H, J = 2.3 Hz), 7.71 (dd, 1H, J = 8.3, 2.3Hz), 7.63 (s, 2H), 7.48 (s, 1H), 6.96 (d, 1H, J = 8.7 Hz), 3.93 (s, 3H),3.65 (p, 1H, J =6.8 Hz), 3.51 (q, 2H, J = 7.3 Hz), 3.18 (t, 2H, J = 6.8Hz), 2.85 (s, 3H), 2.72 (s, 6H), 2.14 (m, 2H), 1.58 (t, 3H, J =7.3 Hz)17-6

385.5333 A 17-7

371.5065 B CDCl3 7.67 (dd, 1H, J = 8.3, 1.9 Hz), 7.57 (d, 1H, J = 2.6Hz), 7.55 (s, 2H), 7.44 (s, 1H), 6.67 (d, 1H, J = 8.3 Hz), 3.96 (s, 3H),3.51 (q, 2H, J = 7.5 Hz), 3.30 (t, 2H, J = 6.4 Hz), 2.64 (t, 2H, J = 6.4Hz), 2.31 (s, 6H), 1.58 (t, 3H, J = 7.4 Hz) 17-8

371.5065 B CDCl3 7.63 (s, 2H), 7.46 (s, 1H), 7.43 (d, 1H, J = 8.0 Hz),7.33 (s, 1H), 6.86 (d, 1H, J = 8.3 Hz), 3.91 (s, 3H), 3.51 (q, 2H, J =7.2 Hz), 3.29 (t, 2H, J = 6.1 Hz), 2.65 (t, 2H, J = 6.3 Hz), 2.29 (s,6H), 1.58 (t, 3H, J = 7.4 Hz) 17-9

390.5088 C CDCl3 7.56-7.27 (m, 10 Hz), 6.65 (d, 1H, J = 8.3 Hz), 4.46(br s, 2H), 3.97 (s, 3H), 3.50 (q, 2H, J = 7.4 Hz), 1.57 (t, 3H, J = 7.4Hz) 17-10

358.4638 B CDCl3 7.65 (d, 1H, J = 8.3 Hz), 7.60 S, 1H), 7.57 (s, 1K),7.55 (s, 1H), 7.44 (s, 1H), 6.68 (d, 1H, J = 8.3 Hz), 4.76 (br s, 2H),3.95 (s, 3H), 3.67 (t, 2H, J = 5.3 Hz), 3.51 (q, 2H, J = 7.2 Hz), 3.42(s, 3H), 3.39 (t, 3H, J = 4.9 Hz), 1.58 (t, 3H, J = 7.1 Hz) 17-11

408.5276 A CDCl3 7.63 (s, 2H), 7.46 (s, 1H); 7.43 (d, 1H, J = 8.0 Hz),7.33 (s, 1H), 6.86 (d, 1H, J = 8.3 Hz), 3.91 (s, 3H), 3.51 (q, 2H, J =7.2 Hz), 3.29 (t, 2H, J = 6.1 Hz), 2.65 (t, 2H, J = 6.3 Hz), 2.29 (s,6H), 1.58 (t, 3H, J = 7.4 Hz) 17-12

427.5701 A CDCl3 7.63 (dd, 1H, J = 8.3, 1.9 Hz), 7.59 (s, 1H), 7.56 (s,2H), 7.44 (s, 1H), 6.66 (d, 1H, J = 8.3 Hz), 5.41 (br s, 1H), 3.97 (s,3H), 3.78 (m, 4H), 3.50 (q, 2H, J = 7.2 Hz), 3.29 (br s, 2H), 2.52 (m,4H), 1.87 (p, 2H, J = 6.4 Hz), 1.58 (t, 3H, J =7.3 Hz) 17-13

385.5333 A CDCl3 7.69 (d, 1H, J = 8.3 Hz), 7.60 (s, 1H), 7.57 (s, 1H),7.53 (s, 1H), 7.43 (s, 1H), 6.67 (d, 1H, J = 8.3 Hz), 3.94 (s, 3H), 3.51(q, 2H, J =7.3 Hz), 3.27 (t, 2H, J = 6.9 Hz), 2.42 (t, 2H, J = 7.0 Hz),2.27 (s, 6H), 1.85 (p, 2H, J =6.8 Hz), 1.58 (t, 3H, J = 7.3 Hz) 17-14

314.4112 B CDCl3 7.68 (dd, 1H, J = 8.2, 1.9 Hz), 7.59 (d, 1H, J = 1.6Hz), 7.58 7.43 (s, 1H), 6.65 (d, 1H, J = 8.2 Hz), 3.94 (s, 3H), 3.50 (q,2H, J =7.4 Hz), 2.93 (s, 3H), 1.58 (t, 3H, J = 7.4 Hz) 17-15

328.438 A CDCl3 7.65 (s, 2H), 7.63 (s, 2H), 7.47 (s, 1H), 7.01 (d, 1H, J= 8.6 Hz), 3.99 (s, 3H), 3.51 (q, 2H, J =7.3 Hz), 2.87 (s, 3H), 1.59 (t,3H, J = 7.3 Hz) 17-16

415.4945 A CDCl3 7.64 (s, 1H), 7.61 (s, 2H), 7.59 (s, 1H), 7.55 (d, 1H,J = 8.3 Hz), 7.42 (s, 2H), 6.95 (d, 2H, J =9.1 Hz), 6.75 (d, 1H, J = 8.3Hz), 3.88 (s, 3H), 3.84 (s, 3H), 3.40 (t, 4H, J = 6.4 Hz), 1.94 (m, 4H)17-17

441.5969 A CDCl3 7.65 (s, 2H), 7.63 (s, 2H), 7.47 (s, 1H), 7.00 (d, 1H,J = 14.4 Hz), 3.96 (s, 3H), 3.70 (t, 4H, J =7.9 Hz), 3.51 (q, 2H, J =12.1 Hz), 3.21 (t, 2H, J = 12.6 Hz), 2.87 (s, 3H), 2.44-2.36 (m, 6H),1.77 (m, 2H), 1.59 (t, 3H, J = 12.3 Hz)

[0314] The compounds shown in the Tables 17 below were synthesizedaccording to any of the procedures described above in combination ofknown conventional chemical synthesis. IC₅₀ classes defined above arelisted in the table. TABLE 17 Ex. Activity No. MOLSTRUCTURE MOLWEIGHTgrade MS NMR 1

331.3802 B (CD3OD) 3.90 (3H, s), 6.92 (1H, d, J = 9.1 Hz), 7.11-7.19(1H, m), 7.32 (1H, s), 7.39-7.51 (4H, m), 7.54 (1H, s), 7.86 (2H, d, J =8.7 Hz), 8.06 (1H, s) 2

431.4549 A (d8-DMSO) 2.52-2.62 (2H, m), 2.65-2.76 (2H, m), 3.90 (3H, s),7.10-7.19 (2H, m), 7.42-7.52 (3H, m), 7.61 (1H, s), 7.79-7.87 (1H, m),8.01 (2H, d, J = 7.9 Hz), 8.32 (1H, s), 8.91 (1H, s), 9.21 (1H, s), 9.47(1H, s) 3

373.4179 A (d8-DMSO) 2.14 (3H, s), 3.89 (3H, s), 7.08-7.19 (2H, m),7.41-7.52 (3H, m), 7.61 (1H, s), 7.78-7.88 (1H, m), 7.95-8.05 (2H, m),8.31 (1H, s), 8.82 (1H, s), 9.16 (1H, s), 9.47 (1H, s) 4

361.4067 C 362 (CDCl3) 3.82 (3H, s), 3.95 (3H, s), 3.99 (3H, s),6.70-6.77 (2H, m), 6.96-7.02 (2H, m), 7.46 (1H, d, J = 1.1 Hz),7.60-7.71 (4H, m), 8.32 (1H, d, J = 3.0 Hz) 5

463.4974 A 464 6

447.498 A 448 7

447.498 A 448 8

523.5987 A 524 9

372.3867 10000 373 10

416.4402 C (CDCl3) d 2.24 (3H, s), 2.36 (3H, s), 3.90 (3H, s), 7.07 (1H,d, J = 8.6 Hz), 7.34-7.45 (6H, m), 7.63 (1H, d, J = 1.2 Hz), 7.75 (1H,d, J = 2.2 Hz), 7.81 (1H, s), 7.89 (1H, dd, J =2.2, 8.6 Hz). 11

404.432 A 405 12

503.6092 A 504 13

432.4861 A 433 14

349.352 10000 350 15

417.4715 C 418 16

374.4026 B 374 (CDCl3) d 3.97 (3H, s), 4.02 (3H, s), 7.04 (1H, d, J =8.4 Hz), 7.17 (1H, d, J = 1 Hz), 7.40 (1H, dd, J =1 Hz, 8.4 Hz),7.46-7.60 (5H, m), 8.11 (1H, s), 8.39 (1H, d, J = 8.4 Hz) 17

499.0359 A 463 (CDCl3) 2.68 (2H, t, J = 7.3 Hz), 2.84 (3H, s), 2.91 (2H,t, J = 7.3 Hz), 2.97 (3H, s), 3.62 (3H, s), 3.80 (3H, s), 7.02 (1H, d, J= 8.5 Hz), 7.34 (1H, d, J = 1.9 Hz), 7.52 (2H, d, J = 8.2 Hz), 7.61 (1H,dd, J = 1.9 Hz, 8.5 Hz), 7.72 (2H, d, J = 8.2 Hz), 8.11 (1H, s), 8.17(1H, d, 18

541.0735 A 505 (CDCl3) 2.70 (2H, t, J = 7.2 Hz), 2.93 (2H, t, J = 7.2Hz), 3.44 (4H, t, J = 5.1 Hz), 3.53 (4H, t, J = 5.1 Hz), 3.62 (3H, s),3.79 (3H, s), 6.99 (1H, d, J = 8.6 Hz), 7.34 (1H, d, J = 1.8 Hz),7.48-7.61 (3H, m), 7.72 (2H, d, J = 8.1 Hz), 8.03 (1H, s), 8.07 (1H, s),8.22 (1H, s). 19

461.5438 A 462 (CDCl3) 1.92-2.04 (1H, m), 2.25-2.31 (1H, m), 2.82-3.02(3H, m), 3.11 (2H, d, J = 7.8 Hz), 3.75 (3H, s), 3.90 (3H, s), 6.86 (1H,d, J = 8.4 Hz), 7.32 (1H, d, J = 2.1 Hz), 7.38 (1H, dd, J = 2.0 Hz, 8.4Hz), 7.47-7.52 (2H, m), 7.59(1H, s), 7.64(1H, s), 7.68 (1H, s). 20

434.5208 A 435 (CDCl3) 2.58 (2H, t, J = 7.7 Hz), 3.06 (2H, t, J = 7.7Hz), 3.75 (3H, s), 3.90 (3H, s), 5.28-5.36 (2H, bs), 6.87 (1H, d, J =8.5 Hz), 7.31 (1H, d, J = 2.0 Hz), 7.36-7.41 (3H, m), 7.61 (1H, s), 7.65(1H, d, J = 1.8 Hz), 7.69 (1H, s). 21

448.5479 A 449 (CDCl3) 2.50 (2H, t, J = 7.9 Hz), 2.78 (3H, d, J = 4.8Hz), 3.05 (2H, t, J = 7.9 Hz), 3.75 (3H, s), 3.90 (3H, s), 5.39-5.40(1H, bs), 6.87 (1H, d, J = 8.5 Hz), 7.29 (1H, d, J = 2.0 Hz), 7.34-7.39(3H, m), 7.59-7.67 (5H, m). 22

389.4131 B (DMSO-d6) d 3.79 (3H, s), 3.84 (3H, s), 7.13 (1H, d, J = 7.5Hz), 7.39 (1H, t, J = 7.5 Hz), 7.61-7.90 (1H, m), 8.43 (1H, s), 10.56(1H, s), 11.74 (1H, s) 23

487.5849 A (DMSO) 2.63 (2H, t, J = 8.4 Hz), 2.93 (2H, t, J = 7.2 Hz),3.26-3.33 (4H, m), 3.63 (3H, s), 3.77 (3H, s), 6.95 (1H, d, J = 8.7 Hz),7.35 (1H, d, J = 1.9 Hz), 7.45 (2H, d, J = 8.3 Hz), 7.51 (1H, dd, J =1.9 Hz, 8.7 Hz), 7.70 (2H, d, J = 8.3 Hz), 7.74 (1H, d, J = 1.5 Hz),7.96 (1H, d, 24

459.5335 A (DMSO) 3.16 (2H, t, J = 8.8 Hz), 3.27 (2H, t, J = 6.8 Hz),3.64 (3H, s), 3.78 (3H, s), 6.95 (1H, d, J = 8.3 Hz), 7.36 (1H, d, J =1.9 Hz), 7.45-7.49 (3H, m), 7.70 (1H, s), 7.73-7.74 (2H, m), 7.98 (1H,s), 7.98 (1H, s). 25

444.4357 A 331 (DMSO) 3.40 (2H, bq), 3.76 (2H, t, J = 6.6 Hz), 3.84 (3H,s), 3.90 (3H, s), 7.06 (1H, d, J = 8.4 Hz), 7.72 (1H, d, J = 2.0 Hz),7.79 (1H, s), 7.83 (1H, dd, J = 2.0 Hz, 8.4 Hz), 7.91 (1H, s), 7.99 (2H,bs), 8.07 (1H, s). 26

345.3796 C 346 (DMSO) 1.59 (3H, s), 3.81 (3H, s), 3.89 (3H, s), 4.00(2H, s), 7.07 (1H, d, J = 8.9 Hz), 7.65 (1H, d, J = 1.4 Hz), 7.78-7.83(3H, m), 7.88 (1H, s). 27

330.3666 A (CDCl3) 1.58 (3H, t, J = 7.1 Hz), 3.52 (2H, q, J = 7.1 Hz),4.04 (3H, s), 7.20 (1H, d, J = 9.0 Hz), 7.52 (1H, s), 7.68 (2H, s), 8.19(1H, dd, J = 2.3, 9.0 Hz), 8.63 (1H, d, 2.3 Hz) 28

358.4202 B (DMSO d6) 1.52 (3H, t, J = 7.5 Hz), 3.53 (2H, q, J = 7.5 Hz),3.83 (3H, s), 3.88 (3H, s), 7.10 (1H, d, J = 8.3 Hz), 7.57 (1H), 7.72(1H), 7.79-7.82 (2H), 7.93 (1H), 8.07 (1H) 29

475.5461 A (DMSO) 1.04 (1H, d, J = 6.0 Hz), 1.09 (3H, d, J = 6.3 Hz),1.17 (3H, d, J = 6.3 Hz), 3.81 (3H, s), 3.86 (3H, s), 4.82-4.87 (1H, m),7.03 (1H, d, J = 8.5 Hz), 7.26 (2H, d, J = 8.2), 7.39-7.40 (1H, m), 7.61(2H, d, J = 8.2 Hz), 7.69 (1H, d, J = 8.2 Hz), 7.70 (1H, s), 7.74-7.81(2H, 30

506.3875 A (DMSO) 2.85-2.90 (1H, m), 3.11-3.15 (1H, m), 3.36-3.78 (3H,m), 3.81 (3H, s), 386 (3H, s), 7.04 (1H, d, J = 8.5 Hz), 7.31 (1H, d, J= 8.2 Hz), 7.60 (1H, s), 7.62 (1H, s), 7.71 (1H, d, J = 8.2 Hz), 7.77(1H, s), 7.86 (1H, d, J = 8.5 Hz), 8.34 (1H, s). 31

414.4272 A (DMSO) 3.82 (3H, s), 3.87 (3H, s), 7.07 (1H, d, J = 8.2 Hz),7.39 (1H, t, J = 7.9 Hz), 7.64-7.70 (4H, m), 7.87 (1H, s), 8.17 (1H, d,J = 7.9 Hz), 8.26 (1H, s), 8.69 (1H, d, J = 8.2 Hz), 11.6 (1H, bs). 32

432.4816 A (CDCl3), 3.00 (6H, s), 3.95 (3H, s), 4.01 (3H, s), 6.87 (1H,d, J = 2.8 Hz), 6.98 (1H, d, J = 8.5 Hz), 7.04 (1H, dd, J = 9.1 Hz, J =2.8 Hz), 7.44 (2H, s), 7.63 (2H, d, J = 4.7 Hz), 7.65 (2H, dd, J = 8.5Hz, J = 1.9 Hz), 7.71 (2H, d, J = 1.9 Hz) 33

404.428 A (CD3OD), 3.89 (3H, s), 3.92 (3H, s), 6.98 (1H, d, J = 2.6 Hz),7.01 (1H, s), 7.04 (1H, s), 7.15 (2H, d, J = 2.6 Hz), 7.36 (2H, s), 7.56(2H, d, J = 1.5 Hz), 7.64 (1H, dd, J = 8.8 Hz, J = 2.3 Hz), 7.71 (2H,s), 7.76 (1H, d, J = 2.3 Hz) 34

331.3733 B 332 (MeOD) 3.89 (3H, s), 3.92 (3H, s), 7.07 (1H, d, J = 9.1Hz), 7.59-7.72 (5H, m), 7.76-7.79 (1H, m), 7.87 (1H, s), 7.91-7.99 (1H,m), 8.00-8.03 (2H, m) 35

345.4001 C 346 (MeOD) 3.85 (3H, s), 3.87 (3H, s), 4.56 (2H, s), 7.03(1H, d, J = 9.0 Hz), 7.23-7.40 (5H, m), 7.57 (1H, d, J = 1.5 Hz),7.66-7.70 (2H, m), 7.79-7.81 (2H, m) 36

361.4031 C 362 (MeOD) 3.75 (3H, s), 3.89 (3H, s), 3.92 (3H, s), 6.91(2H, d, J = 6.6 Hz), 7.07 (1H, d, 8.2 Hz), 7.13 (1H, m), 7.56 (1H, d, J= 1.3 Hz), 7.74-7.77 (2H, m), 7.83 (1H, d, J = 0.63 Hz), 8.37 (2H, d, J= 6.6 Hz) 37

390.4012 A 391 (DMSO d-6) 3.86 (3H, s), 3.90 (3H, s), 7.12 (1H, d, J =8.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 7.690-7.74 (3H, m), 7.91 (1H, s),8.01 (s, 1H), 8.12 (1H, s), 8.51 (1H, d, J = 7.4 Hz), 8.63 (1H, d, J =7.4 Hz), 8.96 (1H, brs). 38

445.4849 A 446 DMSO 15.93 (s, 1H), 10.38 (s, 1H), 8.37 (d, 1H, J = 4.2Hz), 7.72 (s, 1H), 7.58 (s, 1H), 7.41 (d, 1H, J = 1.9 Hz), 7.27 (d, 1H,J = 2.2 Hz), 7.16-7.06 (m, 3H), 4.01 (s, 3H), 3.93 (t, 4H, J = 4.8 Hz),3.19 (t, 4H, J = 4.4 Hz)

[0315] The compounds shown in the Tables 18 below are synthesizedaccording to any of the procedures described above in combination ofknown conventional chemical synthesis. TABLE 1

No. R¹¹ 1

2

3

4

5

6

7

9

10

11

12

13

14

15

Preparation Example 1

[0316] A mixture of the compound synthesized in Example 1 (10.0 mg) andmagnesium stearate (3.0 mg) is granulated with the use of an aqueoussolution of soluble starch (7.0 mg/0.07 ml). The granules are dried andblended with 70.0 mg of lactose and 50.0 mg of corn starch. The blend iscompressed into a tablet.

Preparation Example 2

[0317] The compound synthesized in Example 1 (5.0 mg) and sodiumchloride (20.0 mg) are dissolved in distilled water to obtain a totalvolume of 2.0 ml. The resulting solution was filtered and filled into a2 ml-ampule under a sterile condition. The ampule is sterilized andsealed to give and injection solution.

[0318] (Anaphylactic Bronchoconstriction in Rats)

[0319] 6 Weeks old male Wistar rats are sensitized intravenously (i.v.)with 10 μg mouse anti-DNP IgE, SPE-7, and 1 days later, the rats arechallenged intravenously with 0.3 ml of saline containing 1.5 mg DNP-BSA(30) under anesthesia with urethan (1000 mg/kg, i.p.) and gallamine (50mg/kg, i.v.). The trachea is cannulated for artifical respiration (2ml/stroke, 70 strokes/min). Pulmonary inflation pressure (PIP) isrecorded thruogh a side-arm of cannula connected to pressure transducer.Change in PIP reflect change of both resistance and compliance of thelungs. To evaluate the drugs prepared in Preparation Example 2, the drug(3 mg/kg) is given i.v. 5 min before challenge. The drug of the presentinvention shows strong activity in vivo assays.

1) a compound of the formula:

wherein R¹ represents —OR¹¹, —SR¹¹, —SOR¹¹, —SO₂R¹¹, —NHR¹¹, —NR¹²R¹³ or—CR¹⁴R¹⁵R¹¹, R¹¹ represents H, phenyl carbonyl, thienyl optionallysubstituted by COOR¹¹¹ (R¹¹¹ is H or C₁-C₆ alkyl), pyrimidyl, C₂-C₆alkenyl, imidazolyl optionally substituted by C₁-C₆ alkyl, triazolyloptionally substituted by C₁-C₆ alkyl, tetrazolyl optionally substitutedby C₁-C₆ alkyl, thiadiazolyl optionally substituted by C₁-C₆ alkyl,pyrrolidinyl optionally substituted by C₁-C₆ alkyl, cyclohexenyl, C₁-C₁₀straight- or branched-alkyl optionally substituted by R¹¹², R¹¹³ and/orR¹¹⁴, C₃-C₁₀ cyclo-alkyl optionally substituted by R¹¹², R¹¹³ and/orR¹¹⁴, phenyl optionally substituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷, pyridyloptionally substituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷, or 9-10-memberedunsaturated condensed ring which optionally contains up to 3 heteroatoms selected from the group consisting of N, O and S and optionallysubstitued by R¹¹⁸, R¹¹² represents halogen, amino, —COOR^(112a)(R^(112a) represents H or C₁-C₆ alkyl) —CO—NH—CH₃, —CO—NH—(CH₂)_(p) CN(p=0, 1, 2, 3, 4, 5, or 6), —NH—COOR^(112a), pyrazinyl, tetrazolyl,dihydrothiophenyl, morpholino, piperidino, di(C₁-C₆ alkyl)amino,indolyl, pyridinyl, thiophenyl, or phenyl optionally substituted by oneto three substituents selected from the group consisting of halogen,C₁-C₆ alkyl, hydroxy, C₁-C₆ alkoxy, and trihalogen substituted C₁-C₆alkyl, R¹¹³ represents halogen, hydroxy, or C₁-C₆ alkoxy-carbonyl, R¹¹⁴represents halogen, R¹¹⁵ represents H, halogen, amino, hydroxy, nitro,cyano, C₁-C₆ alkoxy, carboxy, C₁-C₆ alkoxy carbonyl, C₁-C₆ alkylcarbonyl, morpholino-C₁-C₆ alkyl-oxy, caroboxy-C₁-C₆ alkyl-oxy,trihalogen substituted methyl, trihalogen substituted methoxy, C₁-C₁₀straight- or branched-alkyl optionally substituted by R^(115a), C₃-C₁₀cyclo-alkyl optionally substituted by R^(115a), tetrazolyl, amidino,—CON(R^(115b))R^(115c), —SO₂N(R^(115b))R^(115c), —N(R^(115b))R^(115c),—SO₂R^(115d), —SOR^(115d), —SR^(115d), or C₂-C₆ alkenyl optionallysubstituted by COOR^(115e) R^(115a) represents one or two selected fromthe group consisting of carboxy, morpholino, morpholino-carbonyl, amino,hydroxy, cyano, C₁-C₆ alkoxy carbonyl, carbamoyl optionally substitutedby cyano-C₁-C₆ alkyl, methylamino-carbonyl, dimethylamino-carbonyl,—NH—SO₂—CH₃, tetrazolyl, dihydrooxazolyl optionally substituted by C₁-C₆alkyl, and 9-10 membered unsaturated condensed ring containing one Natom optionally substituted by ═O, R^(115b) represents H or C₁-C₆ alkyl,R^(115c) represents H, amino, C₁-C₆ alkylamino, di(C₁-C₆ alkyl)amino,amidino, morpholino-C₁-C₆ alkyl carbonyl, carboxy-C₁-C₆ alkyl carbonyl,or straight- or branched C₁-C₆ alkyl optionally substituted by one ortwo selected from the group consisting of hydroxy, phenyl, morpholino,di(C₁-C₆ alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl substitutedamino, C₁-C₆ alkoxy-carbonyl, and carboxy, or R^(115b) and R^(115c)together with the adjacent N form 5 or 6 membered saturated heterocyclic ring optionally having one N or O atom other than the adjacent Nand optionally substituted by C₁-C₆ alkyl, R^(115d) represents hydroxy,hydroxy C₁-C₆ alkyl, C₁-C₆ alkyl, hydroxy-carbonyl-C₁-C₆ alkyl, or C₁-C₆alkoxy carbonyl C₁-C₆ alkyl, R^(115e) represents hydrogen or C₁-C₆alkyl, R¹¹⁶ represents H, C₁-C₆ alkoxy, C₁-C₆ alkyl, halogen, orcarbamoyl, R¹¹⁷ represents H, halogen, or C₁-C₆ alkoxy, R¹¹⁸ representsone to three substituents selected from the group consisting of C₁-C₆alkyl, amino, C₁-C₆ alkoxy, —COOR^(118a) (R^(118a) is H or C₁-C₆ alkyl),and ═O, R¹² represents C₁-C₆ alkyl, —(CH₂)_(q)—OH, —(CH₂)_(q)—CN (q=0,1, 2, 3, 4, 5, or 6), —CO—C₁-C₆ alkyl) , or —C₂-C₆ alkenyl, R¹³ isidentical to R¹¹, or R¹² and R¹³ together with the adjacent N atom form4-6 membered saturated heterocyclic ring which may or may not contain 1heteroatom other than the adjacent N atom selected from the groupconsisting of O, N, and S the 4-6 membered heterocyclic ring optionallyform spiro with dioxacyclopentane, or is optionally fused with benzene,and/or is optionally substituted by one or two substituents selectedfrom the group consisting of C₁-C₆ alkyl carbonyl, C₁-C₆ alkyl, hydroxy,hydroxy C₁-C₆ alkyl, carboxyl, C₁-C₆ alkoxy carbonyl, carbamoyl, phenyl,halogen substituted phenyl, C₁-C₆ alkoxy substituted phenyl, C₁-C₆ alkylsubstituted phenyl, nitro phenyl, hydroxy phenyl, C₁-C₆ alkyl carbonylphenyl, C₁-C₆ alkoxy carbonyl phenyl, pyridyl optionally substituted byCF₃, pyrimidyl, C₃₋₇ cycloalkyl, dioxolanyl, piperidino, halogensubstituted phenyl carbonyl, furyl carbonyl, cyano, dimethylamino,benzyl, oxo residue, piperonyl methyl, halogen substituted diphenylmethyl, and trifluorocarbonyl amino, R¹⁴ and R¹⁵ are identical ordifferent and represent H, C₁-C₁₀ alkyl, hydroxy, hydroxy C₁-C₆ alkyl,cyano C₁-C₆ alkyl, C₃-C₁₀ cycloalkyl, C₂-C₁₀ alkenyl, or C₁-C₆ alkylcarbonyl; Y is CH or N; R² is H, C₁-C₆ alkyl, carbamoyl, or —COOR²¹,wherein R²¹ is H or C₁-C₆ alkyl; R³ is thienyl, pyridyl optionallysubstituted by halogen or C₁-C₆ alkoxy, naphthyl optionally substitutedby C₁-C₆ alkoxy, dioxane fused phenyl, dioxacyclopentane fused phenyl,or phenyl optionally substituted by one to three substituents selectedfrom the group consisting of halogen, C₁-C₆ alkyl, nitro, amino,hydroxy, C₁-C₆ alkylthio, —OR³¹, —OR³², —NR³³R³⁴, and —SO₂R³⁵, whereinR³¹ and R³² are identical or different and represent C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxy carbonyl, C₂-C₆ alkenyl, di(C₁-C₆ alkyl) aminocarbonyl, C₁-C₆ alkyl amino carbonyl, —SO₂-R³¹¹, straight- orbranched-C₁-C₆ alkyl optionally substituted by R³¹², or cyclo-C₃-C₇alkyl optionally substituted by R³¹², R³¹¹ represents C₁-C₆ alkyl,amino, di(C₁-C₆ alkyl) amino C₁-C₆ alkyl amino, C₁-C₆ alkoxy carbonylC₁-C₆ alkyl amino, or 5-6 membered saturated hetero ring containing upto 2 heteroatoms of N, S, and/or O and optionally substituted by C₁-C₆alkyl or carboxy, R³¹² represents C₁-C₆ alkoxy, halogen, phenyloptionally substituted by C₁-C₆ alkoxy, di(C₁-C₆ alkyl) amino, C₁-C₆alkyl and hydroxy C₁-C₆ alkyl substituted amino, or 5-6 memberedsaturated hetero cyclic ring containing up to 2 heteroatoms of N, S,and/or O and optionally substituted by one or three substituentsselected from the group consisting of C₁-C₆ alkyl, carbamoyl, anddi(C₁-C₆ alkyl)amino, R³³ represents H or C₁-C₆ alkyl, R³⁴ representscarboxy C₁-C₆ alkyl carbonyl, C₁-C₆ alkyl carbonyl, or C₁-C₆ alkyloptionally substituted by R³⁴¹, wherein R³⁴¹ represents dimethylamino,C₁-C₆ alkoxyl, morpholino, phenyl, C₁-C₆ alkyl substituted piperazino,oxopyrrolidino, or imidazolyl, or —N R³³R³⁴ forms 5-6-membered saturatedhetero cyclic ring optionally containing one more hetero atom selectedfrom the group consisting of N, S, and O and optionally substituted byC₁-C₆ alkyl, R³⁵ represents amino, di(C₁-C₆ alkyl)amino C₁-C₆ alkylamino, piperazino optionally substituted by hydroxy C₁-C₆ alkyl or C₁-C₆alkyl, C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl amino, morpholino, piperidinooptionally substituted by carboxy or C₁-C₆ alkyl, or hydroxy C₁-C₆ alkylamino, or its tautomeric or stereoisomeric form, or its physiologicallyacceptable salt. 2) The compound as claimed in claim 1, wherein R¹represents —OR¹¹, —SR¹¹, —NHR¹¹, or —NR¹²R¹³ R¹¹ represents H, phenylcarbonyl, thienyl optionally substituted by COOR¹¹¹ (R¹¹¹ is H or C₁-C₆alkyl), pyrimidyl, C₂-C₆ alkenyl, imidazolyl optionally substituted byC₁-C₆ alkyl, triazolyl optionally substituted by C₁-C₆ alkyl, tetrazolyloptionally substituted by C₁-C₆ alkyl, thiadiazolyl optionallysubstituted by C₁-C₆ alkyl, pyrrolidinyl optionally substituted by C₁-C₆alkyl, cyclohexenyl, C₁-C₁₀ straight- or branched-alkyl optionallysubstituted by R¹¹², R¹¹³ and/or R¹¹⁴, C₃-C₁₀ cyclo-alkyl optionallysubstituted by R¹¹², R¹¹³ and/or R¹¹⁴, phenyl optionally substituted byR¹¹⁵, R¹¹⁶, and/or R¹¹⁷, pyridyl optionally substituted by R¹¹⁵, R¹¹⁶,and/or R¹¹⁷, or 9-10-membered unsaturated condensed ring whichoptionally contains up to 3 hetero atoms selected from the groupconsisting of N and S and optionally substituted by R¹¹⁸, R¹¹²represents halogen, amino, —COOR^(112a) (R^(112a) represents H or C₁-C₆alkyl), —CO—NH—CH₃, —CO—NH—(CH₂)_(p) CN, —NH—COOR^(112a), pyrazinyl,tetrazolyl, dihydrothiophenyl, morpholino, piperidino, di(C₁-C₆alkyl)amino, indolyl, pyridinyl, thiophenyl, or phenyl optionallysubstituted by one substituent selected from the group consisiting ofhalogen, hydroxy, C₁-C₆ alkoxy, and trihalogen substituted methyl, R¹¹³represents halogen, hydroxy, or C₁-C₆ alkoxy-carbonyl, R¹¹⁴ representshalogen, R¹¹⁵ represents H, halogen, amino, hydroxy, nitro, cyano,carboxy, C₁-C₆ alkoxycarbonyl, C₁-C₆ alkoxy, C₁-C₆ alkyl carbonyl,morpholino-C₁-C₆ alkyl-oxy, carboxy-C₁-C₆ alkyl-oxy, trihalogensubstituted methyl, trihalogen substituted methoxy, C₁-C₁₀ straight- orbranched-alkyl optionally substituted by R^(115a), C₃-C₁₀ cyclo-alkyloptionally substituted by R^(115a), tetrazolyl, amidino,—CON(R^(115b))R^(115c), —SO₂N(R^(115b))R^(115c), —N(R^(115b))R^(115c),—SO₂R^(115d), —SOR^(115d), —SR^(115d), or C₂-C₆ alkenyl optionallysubstituted by COOR^(115e), R^(115a) represents one or two selected fromthe group consisting of carboxy, morpholino, morpholino-carbonyl, amino,hydroxy, cyano, C₁-C₆ alkoxy carbonyl, carbamoyl optionally substitutedby cyano-C₁-C₆ alkyl, methylamino-carbonyl, dimethylamino-carbonyl,—NH—SO₂—CH₃, tetrazolyl, dihydrooxazolyl optionally substituted by C₁-C₆alkyl, and 9-10 membered unsaturated condensed ring containing one Natom optionally substituted by ═O, R^(115b) represents H or C₁-C₆ alkyl,R^(115c) represents H, amino, C₁-C₆ alkyl amino, di(C₁-C₆ alkyl)amino,amidino, morpholino-C₁-C₆ alkyl carbonyl, carboxy-C₁-C₆ alkyl carbonyl,or straight- or branched C₁-C₆ alkyl optionally substituted by one ortwo selected from the group consisting of hydroxy, phenyl, morpholino,di(C₁-C₆ alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl substitutedamino, C₁-C₆ alkoxy-carbonyl, and carboxy, or R^(115b) and R^(115c)together with the adjacent N form 5 or 6 membered saturated hetero ringoptionally having one N or O atoms other than the adjacent N andoptionally substituted by C₁-C₆ alkyl, R^(115d) represents hydroxy,hydroxy C₁-C₆ alkyl, C₁-C₆ alkyl, hydroxy-carbonyl-C₁-C₆ alkyl, or C₁-C₆alkoxy carbonyl C₁-C₆ alkyl, R^(115e) represents hydrogen or C₁-C₆alkyl, R¹¹⁶ represents H, C₁-C₆ alkoxy, C₁-C₆ alkyl, halogen, orcarbamoyl, R¹¹⁷ represents H, halogen, or C₁-C₆ alkoxy, R¹¹⁸ representsone to three substituents selected from the group consisting of C₁-C₆alkyl, amino, C₁-C₆ alkoxy, COOR^(118a) (H or C₁-C₆ alkyl), and ═O R¹²represents C₁-C₆ alkyl, —(CH₂)_(q)—OH, —(CH₂)_(q)—CN (q=0, 1, 2, 3, 4,5, or 6), —CO—C₁-C₆ alkyl), or —C₂-C₆ alkenyl (—CH₂—CH═CH₂), R¹³ isidentical to R¹¹, or R¹² and R¹³ together with the adjacent N atom form4-6 membered saturated heterocyclic ring which may or may not contain 1heteroatom other than the adjacent N atom selected from the groupconsisting of O, N, and S, the 4-6 membered heterocyclic ring optionallyform spiro with dioxacyclopentane, or is optionally fused with benzene,and/or is optionally substituted by one or two substituents selectedfrom the group consisting of C₁-C₆ alkyl, C₁-C₆ alkyl carbonyl, hydroxy,hydroxy C₁-C₆ alkyl, carboxyl, C₁-C₆ alkoxy carbonyl, carbamoyl, phenyl,halogen substituted phenyl, C₁-C₆ alkoxy substituted phenyl, C₁-C₆ alkylsubstituted phenyl, nitro phenyl, hydroxy phenyl, C₁-C₆ alkyl carbonylphenyl, C₁-C₆ alkoxy carbonyl phenyl, pyridyl optionally substituted byCF₃, pyrimidyl, C₃₋₇ cycloalkyl, dioxolanyl, piperidino, halogensubstituted phenyl carbonyl, furyl carbonyl, cyano, dimethylamino,benzyl, oxo residue, piperonyl methyl, halogen substituted diphenylmethyl, and trifluorocarbonyl amino, Y is CH or N; R² is H C₁-C₆ alkyl,or carbamoyl; R³ is thienyl, pyridyl optionally substituted by halogenor C₁-C₆ alkoxy, dioxane fused phenyl, dioxacyclopentane fused phenyl,or phenyl optionally substituted by one to three substituents selectedfrom the group consisting of halogen, C₁-C₆ alkyl, nitro, amino,hydroxy, C₁-C₆ alkylthio, —OR³¹, —OR³², —NR³³R³⁴, and —SO₂R³⁵, whereinR³¹ and R³² are identical or different and represent nitro, C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxy carbonyl, C₂-C₆alkenyl, di(C₁-C₆ alkyl) aminocarbonyl, C₁-C₆ alkyl amino carbonyl, —SO₂—R³¹¹, straight- orbranched-C₁-C₆ alkyl optionally substituted by R³¹², or cyclo-C₃-C₇alkyl optionally substituted by R³¹², R³¹¹ represents C₁-C₆ alkyl,amino, di(C₁-C₆ alkyl) amino C₁-C₆ alkyl amino, C₁-C₆ alkoxy carbonylC₁-C6 alkyl amino, 5-6 membered saturated hetero ring containing up to 2heteroatoms of N, S, and/or O and optionally substituted by C₁-C₆ alkylor carboxy, R³¹² represents one selected from the group consisting ofC₁-C₆ alkoxy, halogen, phenyl optionally substituted by C₁-C₆ alkoxy,di(C₁-C₆ alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl substitutedamino, or 5-6 membered saturated hetero cyclic ring containing up to 2heteroatoms of N, S, and/or O and optionally substituted by C₁-C₆ alkyl,carbamoyl, or di(C₁-C₆ alkyl)amino, R³³ represents H or C₁-C₆ alkyl, R³⁴represents carboxy C₁-C₆ alkyl carbonyl, C₁-C₆ alkyl carbonyl, or C₁-C₆alkyl optionally substituted by R³⁴¹, wherein R³⁴¹ representsdimethylamino, C₁-C₆ alkoxyl, morpholino, phenyl, C₁-C₆ alkylsubstituted piperazino, oxopyrrolidino, or imidazolyl, or —N R³³R³⁴ formmorpholino optionally substituted by C₁-C₆ alkyl, thiazinano optionallysubstituted by C₁-C₆ alkyl, piperidino optionally substituted by C₁-C₆alkyl, or pyrrolidino optionally substituted by C₁-C₆ alkyl, R³⁵represents amino, di(C₁-C₆ alkyl)amino C₁-C₆ alkyl amino, hydroxy C₁-C₆alkyl amino, C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl amino, morpholino,piperazino optionally substituted by hydroxy C₁-C₆ alkyl or C₁-C₆ alkyl,or piperidino optionally substituted by carboxy, or its tautomeric orstereoisomeric form, or its physiologically acceptable salt. 3) Thecompound as claimed in claim 1, wherein R¹ represents —OR¹¹, —SR¹¹, or—NHR¹¹ R¹¹ represents phenyl optionally substituted by R¹¹⁵, R¹¹⁶,and/or R¹¹⁷, pyridyl optionally substituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷,or 9-10-membered unsaturated condensed ring which optionally contains upto 3 N atoms and optionally substitued by R¹¹⁸ R¹¹⁵ represents H,halogen, amino, hydroxy, nitro, cyano, carboxy, C₁-C₆ alkoxycarbonyl,C₁-C₆ alkoxy, C₁-C₆ alkyl carbonyl, morpholino-C₁-C₆ alkyl-oxy,carboxy-C₁-C₆ alkyl-oxy, trihalogen substituted methyl, trihalogensubstituted methoxy, C₁-C₁₀ straight- or branched-alkyl optionallysubstituted by R^(115a), C₃-C₁₀ cyclo-alkyl optionally substituted byR^(115a), tetrazolyl, amidino, —CON(R^(115b))R^(115c),—SO₂N(R^(115b))R^(115c), —N(R^(115b))R^(115c), —SO₂R^(115d),—SOR^(115d), —SR^(115d), or C₂-C₆ alkenyl optionally substituted byCOOR^(115e), R^(115a) represents one or two selected from the groupconsisting of morpholino, morpholino-carbonyl, amino, hydroxy, cyano,C₁-C₆ alkoxy carbonyl, carbamoyl, methylamino-carbonyl,dimethylamino-carbonyl, —NH—SO₂—CH₃, dihydrooxazolyl optionallysubstituted by C₁-C₆ alkyl, and 9-10 membered unsaturated condensed ringcontaining one N atom optionally substituted by ═O, R^(115b) representsH or C₁-C₆ alkyl, R^(115c) represents H, amino, amidino,morpholino-C₁-C₆ alkyl carbonyl, carboxy-C₁-C₆ alkyl carbonyl, orstraight- or branched C₁-C₆ alkyl optionally substituted by one or twoselected from the group consisting of hydroxy, phenyl, morpholino,di(C₁-C₆ alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl substitutedamino, C₁-C₆ alkoxy-carbonyl, and carboxy, or R^(115b) and R^(115c)together with the adjacent N form 5 or 6 membered saturated heterocyclic ring optionally having one N or O atoms other than the adjacent Nand optionally substituted by C₁-C₆ alkyl, R^(115d) representsC₁-C₆alkyl, hydroxy, hydroxy C₁-C₆ alkyl, hydroxy-carbonyl-C₁-C₆ alkyl,or C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl, R^(115e) represents hydrogen orC₁-C₆ alkyl R¹¹⁶ represents H, C₁-C₆ alkoxy, C₁-C₆ alkyl, halogen, orcarbamoyl, R¹¹⁷ represents H, halogen, or C₁-C₆ alkoxy R¹¹⁸ representsC₁-C₆ alkyl, amino, C₁-C₆ alkoxy, COOR^(118a) (R^(118a) is H or C₁-C₆alkyl), or ═O (mono or di), Y is CH or N; R² is H; R³ is phenyloptionally substituted by two substituents selected from the groupconsisting of —OR³¹, —OR³², and —NR³³R³⁴, wherein R³¹ and R³² areidentical or different and represent straight- or branched-C₁-C₆ alkyloptionally substituted by R³¹², cyclo-C₃-C₇ alkyl optionally substitutedby R³¹², R³¹² represents one selected from the group consisting of C₁-C₆alkoxy, halogen, phenyl optionally substituted by C₁-C₆ alkoxy, di(C₁-C₆alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl substituted amino, or5-6 membered saturated hetero cyclic ring containing up to 2 heteroatomsof N, S, and/or O and optionally substituted by C₁-C₆ alkyl, carbamoyl,or di(C₁-C₆ alkyl)amino, R³³ represents H, or C₁-C₆ alkyl, R³⁴represents C₁-C₆ alkyl optionally substituted by C₁-C₆ alkoxyl, or —NR³³R³⁴ forms morpholino optionally substituted by C₁-C₆ alkyl, or itstautomeric or stereoisomeric form, or its physiologically acceptablesalt. 4) The compound as claimed in claim 1 selected from the groupconsisting of the following compounds:[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]-(1H-indazol-6-yl)-amine;2-[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzamide;2-[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-5-methoxy-benzamide;2-[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzenesulfonamide;[7-(3,4-Dimethoxy-phenyl)-[1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-(1H-indazol-6-yl)-amide;4-Amino-2-[7-(3,4-dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzamide;(7-(3-methoxy-4-[(2-methoxy-ethyl)-methyl-amino]-phenyl)-imidazo[1,2-c]pyrimidin-5-yl)-(4-methoxy-phenyl)-amine;[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]-p-tolyl-amine;(2-Methanesulfonyl-phenyl)-(7-(3-methoxy-4-[(2-methoxy-ethyl)-methyl-amino]-phenyl)-imidazo[1,2-c]pyrimidin-5-yl)-amine;2-[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamide;2-[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-benzamide;2-Methanesulfonyl-phenyl)-[7-(3-methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]-amine;4-[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-phenol;[7-(3-Methoxy-4-morpholin-4-yl-phenyl)-imidazo[1,2-c]pyrimidin-5-yl]-(4-methoxy-phenyl)-amine;and2-[7-(3,4-Dimethoxy-phenyl)-imidazo[1,2-c]pyrimidin-5-ylamino]-nicotinamideor its tautomeric or stereoisomeric form, or its physiologicallyacceptable salt. 5) A process for the preparation of the compoundsaccording to claims 1, comprising that the compounds of the generalformula (II)

in which Y is CH or N; R² is H, C₁-C₆ alkyl, carbamoyl, or —COOR²¹wherein R²¹ is H or C₁-C₆ alkyl; R³ is thienyl, pyridyl optionallysubstituted by halogen or C₁-C₆ alkoxy, naphthyl optionally substitutedby C₁-C₆ alkoxy, dioxane fused phenyl, dioxacyclopentane fused phenyl,or phenyl optionally substituted by one to three substituents selectedfrom the group consisting of halogen, C₁-C₆ alkyl, nitro, amino,hydroxy, C₁-C₆ alkylthio, —OR³¹, —OR³², —NR³³R³⁴, and —SO₂R³⁵, whereinR³¹ and R³² are identical or different and represent C₁-C₆ alkylcarbonyl, C₁-C₆ alkoxy carbonyl, C₂-C₆alkenyl, di(C₁-C₆ alkyl) aminocarbonyl, C₁-C₆ alkyl amino carbonyl, —SO₂—R³¹¹, straight- orbranched-C₁-C₆ alkyl optionally substituted by R³¹², or cyclo-C₃-C₇alkyl optionally substituted by R³¹², R³¹¹ represents C₁-C₆ alkyl,amino, di(C₁-C₆ alkyl) amino C₁-C₆ alkyl amino, C₁-C₆ alkoxy carbonylC₁-C₆ alkyl amino, 5-6 membered saturated hetero cyclic ring containingup to 2 heteroatoms of N, S, and/or O and optionally substituted byC₁-C₆ alkyl or carboxy, R³¹² represents C₁-C₆ alkoxy, halogen, phenyloptionally substituted by C₁-C₆ alkoxy, di(C₁-C₆ alkyl) amino, C₁-C₆alkyl and hydroxy C₁-C₆ alkyl substituted amino, or 5-6 memberedsaturated hetero cyclic ring containing up to 2 heteroatoms of N, S,and/or O and optionally substituted by one or three substituentsselected from the group consistiong of C₁-C₆ alkyl, carbamoyl, anddi(C₁-C₆ alkyl)amino, R³³ represents H or C₁-C₆ alkyl, R³⁴ representscarboxy C₁-C₆ alkyl carbonyl, C₁-C₆ alkyl carbonyl, C₁-C₆ alkyloptionally substituted by R³⁴¹, wherein R³⁴¹ represents dimethylamino,C₁-C₆ alkoxyl, morpholino, phenyl, C₁-C₆ alkyl substituted piperazino,oxopyrrolidino, or imidazolyl, or —N R³³R³⁴ forms 5-6-membered saturatedhetero cyclic ring optionally containing one more hetero atom selectedfrom the group consisting of N, S, and O and optionally substituted byC₁-C₆ alkyl, R³⁵ represents amino, di(C₁-C₆ alkyl)amino C₁-C₆ alkylamino, piperazino optionally substituted by hydroxy C₁-C₆ alkyl or C₁-C₆alkyl, C₁-C₆ alkoxy carbonyl C₁-C₆ alkyl amino, morpholino, piperidinooptionally substituted by carboxy or C₁-C₆ alkyl, or hydroxy C₁-C₆ alkylamino; and L represent a leaving group are reacted with compounds of thegeneral formula (III) HR¹  (III) in which R¹ represents —OR¹¹, —SR¹¹,—SOR¹¹, —SO₂R¹¹, —NHR¹¹, —NR¹²R¹³ or —CR¹⁴R¹⁵R¹¹, R¹¹ represents H,phenyl carbonyl, thienyl optionally substituted by COOR¹¹¹(R¹¹¹ is H orC₁-C₆ alkyl), pyrimidyl, C₂-C₆ alkenyl, imidazolyl optionallysubstituted by C₁-C₆ alkyl, triazolyl optionally substituted by C₁-C₆alkyl, tetrazolyl optionally substituted by C₁-C₆ alkyl, thiadiazolyloptionally substituted by C₁-C₆ alkyl, pyrrolidinyl optionallysubstituted by C₁-C₆ alkyl, cyclohexenyl, C₁-C₁₀ straight- or branched-or cyclo-alkyl optionally substituted by R¹¹², R¹¹³ and/or R¹¹⁴, phenyloptionally substituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷, pyridyl optionallysubstituted by R¹¹⁵, R¹¹⁶, and/or R¹¹⁷, or 9-10-membered unsaturatedcondensed ring which optionally contains up to 3 hetero atoms selectedfrom the group consisting of N, O and S and optionally substitued byR¹¹⁸ R¹¹² represents halogen, amino, —COOR^(112a) (R^(112a) represents Hor C₁-C₆ alkyl) —CO—NH—CH₃, —CO—NH—(CH₂)_(p)CN (p=0, 1, 2, 3, 4, 5, or6), —NH—COOR^(112a), pyrazinyl, tetrazolyl, dihydrothiophenyl,morpholino, piperidino, di(C₁-C₆ alkyl)amino, indolyl, pyridinyl,thiophenyl, or phenyl optionally substituted by one to threesubstituents selected from the group consisting of halogen, C₁-C₆ alkyl,hydroxy, C₁-C₆ alkoxy, and trihalogen substituted C₁-C₆ alkyl, R¹¹³represents halogen, hydroxy, or C₁-C₆ alkoxy-carbonyl, R¹¹⁴ representshalogen, R¹¹⁵ represents H, halogen, amino, hydroxy, nitro, cyano,C₁-C₆alkoxy, carboxy, C₁-C₆ alkoxy carbonyl, C₁-C₆ alkyl carbonyl,morpholino-C₁-C₆ alkyl-oxy, caroboxy-C₁-C₆ alkyl-oxy, trihalogensubstituted methyl, trihalogen substituted methoxy, C₁-C₁₀ straight- orbranched-alkyl optionally substituted by R^(115a), C₃-C₁₀ cyclo-alkyloptionally substituted by R^(115a), tetrazolyl, amidino,—CON(R^(115b))R^(115c), —SO₂N(R^(115b))R^(115c), —N(R^(115b))R^(115c),—SO₂R^(115d), —SOR^(115d), —SR^(115d), or C₂-C₆ alkenyl optionallysubstituted by COOR^(115e) R^(115a) represents one or two selected fromthe group consisting of carboxy, morpholino, morpholino-carbonyl, amino,hydroxy, cyano, C₁-C₆ alkoxy carbonyl, carbamoyl optionally substitutedby cyano-C₁-C₆ alkyl, methylamino-carbonyl, dimethylamino-carbonyl,—NH—SO₂—CH₃, tetrazolyl, dihydrooxazolyl optionally substituted by C₁-C₆alkyl, and 9-10 membered unsaturated condensed ring containing one Natom optionally substituted by ═O, R^(115b) represents H or C₁-C₆ alkyl,R^(115c) represents H, amino, C₁-C₆ alkylamino, di(C₁-C₆ alkyl)amino,amidino, morpholino-C₁-C₆ alkyl carbonyl, carboxy-C₁-C₆ alkyl carbonyl,or straight- or branched C₁-C₆ alkyl optionally substituted by one ortwo selected from the group consisting of hydroxy, phenyl, morpholino,di(C₁-C₆ alkyl) amino, C₁-C₆ alkyl and hydroxy C₁-C₆ alkyl substitutedamino, C₁-C₆ alkoxy-carbonyl, and carboxy, or R^(115b) and R^(114c)together with the adjacent N form 5 or 6 membered saturated heterocyclic ring optionally having one N or O atoms other than the adjacent Nand optionally substituted by C₁-C₆ alkyl, R^(115d) represents hydroxy,hydroxy C₁-C₆alkyl, C₁-C₆ alkyl, hydroxy-carbonyl-C₁-C₆ alkyl, or C₁-C₆alkoxy carbonyl C₁-C₆ alkyl, R^(115e) represents hydrogen or C₁-C₆alkyl, R¹¹⁶ represents H, C₁-C₆ alkoxy, C₁-C₆ alkyl, halogen, orcarbamoyl, R¹¹⁷ represents H, halogen, or C₁-C₆ alkoxy, R¹¹⁸ representsone to three substituents selected from the group consisting of C₁-C₆alkyl, amino, C₁-C₆ alkoxy, —COOR^(118a) (R^(118a) is H or C₁-C₆ alkyl),and ═O, R¹² represents C₁-C₆ alkyl, —(CH₂)_(q)—OH, —(CH₂)_(q)—CN (q=0,1, 2, 3, 4, 5, or 6), —CO—C₁C₆ alkyl, or —C₂-C₆ alkenyl, R¹³ isidentical to R¹¹, or R¹² and R¹³ together with the adjacent N atom form4-6 membered saturated heterocyclic ring which may or may not contain 1heteroatom other than the adjacent N atom selected from the groupconsisting of O, N, and S, the 4-6 membered heterocyclic ring optionallyforms spiro with dioxacyclopentane, or is optionally fused with benzene,and/or is optionally substituted by one or two substituents selectedfrom the group consisting of C₁-C₆ alkyl carbonyl, C₁-C₆ alkyl, hydroxy,hydroxy C₁-C₆ alkyl, carboxyl, C₁-C₆ alkoxy carbonyl, carbamoyl, phenyl,halogen substituted phenyl, C₁-C₆ alkoxy substituted phenyl, C₁-C₆ alkylsubstituted phenyl, nitro phenyl, hydroxy phenyl, C₁-C₆ alkyl carbonylphenyl, C₁-C₆ alkoxy carbonyl phenyl, pyridyl optionally substituted byCF₃, pyrimidyl, C₃₋₇ cycloalkyl, dioxolanyl, piperidino, halogensubstituted phenyl carbonyl, furyl carbonyl, cyano, dimethylamino,benzyl, oxo residue, piperonyl methyl, halogen substituted diphenylmethyl, and trifluorocarbonyl amino, R¹⁴ and R¹⁵ are identical ordifferent and represent H, C₁-C₁₀ alkyl, hydroxy, hydroxy C₁-C₆ alkyl,cyano C₁-C₆ alkyl, C₃-C₁₀ cycloalkyl, C₂-C₁₀ alkenyl (—CH₂—CH═CH₂), orC₁-C₆ alkyl carbonyl; in inert solvents, if appropriate in the presenceof a base and/or in the presence of auxiliary. 6) A medicamentcomprising the compound as claimed in claim 1 or it tautomeric orstereoisomeric form or its physiologically acceptable salt as an activeingredient. 7) A medical composition comprising the compound as claimedin claim 1 or it tautomeric or stereoisomeric form or itsphysiologically acceptable salt together with one or morepharmaceutically acceptable excipients. 8) A method of treating diseasesassociated with Syk tyrosine kinase activity which comprisesadministering to a patient an effective amount of the compound asclaimed in claim 1 or it tautomeric or stereoisomeric form or itsphysiologically acceptable salt. 9) A method of treating allergicdiseases selected from the group consisting of asthma, allergicrhinitis, atopic dermatitis, food allergy, contact allergy, hives,conjunctivitis and vernal catarrh which comprises administering to apatient an effective amount of a compound as claimed in claim 1 or itstautomeric or stereoisomeric form or its physiologically acceptablesalt. 10) A method to suppress immune response comprises administeringto a patient an effective amount of a compound as claimed in claim 1 orits tautomeric or stereoisomeric form or its physiologically acceptablesalt. 11) A method of treating coagulation comprises administering to apatient an effective amount of a compound as claimed in claim 1 or itstautomeric or stereoisomeric form or its physiologically acceptablesalt. 12) A method of treating tumor comprises administering to apatient an effective amount of a compound as claimed in claim 1 or itstautomeric or stereoisomeric form or its physiologically acceptablesalt. 13) Use of the compound as claimed in claim 1 or its tautomeric orstereoisomeric form or its physiologically acceptable salt for thepreparation of medicaments. 14) Use according to claim 13 for thepreparation of medicaments for the treatment and prevention of diseasesassociated with Syk tyrosine kinase activity. 15) Use according to claim13 for the preparation of medicaments for the treatment and preventionof allergic diseases selected from the group consisting of asthma,allergic rhinitis, atopic dermatitis, food allergy, contact allergy,hives, conjunctivitis and vernal catarrh. 16) Use according to claim 13for the preparation of medicaments for immunesuppression. 17) Useaccording to claim 13 for the preparation of medicaments for thetreatment and prevention of coagulation. 18) Use according to claim 13for the preparation of medicaments for the treatment and prevention oftumor.